臺灣博碩士論文加值系統

前言：蚜蟲為吸取植物汁液之半翅目昆蟲，同時為許多植物病毒傳播載體。蚜蟲生活史能藉由行孤雌胎生生殖模式大量快速產生後代；同時，也可利用有性卵生生殖模式擴增基因多樣性。無性及有性蚜蟲皆具有的重要的初級內共生菌能幫助蚜蟲合成生命所需之必需胺基酸。擁有上述特色之豌豆蚜 (Acyrthosiphon pisum)，在 2010 年全基因體解序後進而成為新興昆蟲模式物種。因此，本篇研究目的為探究在孤雌胎生豌豆蚜胚胎早期發育的兩個發育事件：(1) 前後與背腹體軸之形成；與 (2) 內共生菌調控生殖發育。

結果 (I) 前後軸形成：在豌豆蚜已知 Aphunchback (Aphb; 其為果蠅 hunchback (hb) 同源基因) 訊息核糖核酸 (mRNA) 能聚集在卵母細胞與多核囊胚前端，推測 Aphb 前端聚集可能特化無性胎生豌豆蚜前端體軸形成。為了瞭解ApHb 蛋白分佈是否與 Aphb mRNA 不對稱分佈相同，參與胚胎前軸形成，因此， 解剖取得豌豆蚜無性微卵管後，利用純化後的抗 ApHb 蛋白抗體偵測其表現。實驗結果發現早期表現之 ApHb 蛋白為均質表現在卵母細胞與多核囊胚，與 Aphb mRNA 表現形式不同，由此推測 ApHb 蛋白可能不參與前端體軸決定。然而，Aphb mRNA 與 ApHb 皆會表現在胚胎神經母細胞，顯示 Aphb 在蚜蟲神經發育仍具有保守性角色，與其他昆蟲 hb 同源基因一致。特別的是，不論是偵測 Aphb 或 ApHb 表現，皆發現非預期表現在所有胚胎時期的無姓胎生蚜蟲生殖細胞；此 hb生殖表現形式並未在其他昆蟲被報導過，因此，Aphb 表現在無性胎生蚜蟲的生殖發育可能具有新的功能。偵測在其他昆蟲高度保守的後端決定基因 cad 之蚜蟲的同源基因 Apcad 發現，顯示其 mRNA 並未在卵母細胞及多核囊胚後端表現；Apcad 直到胚胎細胞化後，才表現在胚胎後端。由於 Apcad 缺乏早期表現在卵母細胞與多核胚胎之現象推測 Apcad 參與蚜蟲胚胎後端發育，但不參與後軸特化。

結果 (II) 背腹軸形成：在研究背腹體軸如何被建立，我使用參與果蠅背腹體軸決定相關基因在蚜蟲的同源基因，偵測這些同源基因表現是否不對稱表現，是否能驅動無性胎生豌豆蚜胚胎背腹體軸特化。蚜蟲四個果蠅 decapentaplegic (dpp) 同源基因 (Apdpp1–4) 都均質表現在整個蛋腔，與果蠅 dpp 基因能不對稱分佈在蛋腔背側之現象相異。雖然我尚未製作抗體偵測 ApDpp1–4 蛋白的分佈；然而，磷酸化的 Mothers Against Decapentaplegic (pMad) 蛋白—Dpp 活性指標因子與 Apzen (果蠅 zerknüllt (zen) 同源基因)—胚外膜 (在胚胎背側形成) 的標記因子；此二者皆會不對稱表現在 Apsog (果蠅 short gastrulation (sog) 的同源基因) mRNA 表現位置的對側。pMad/zen 與 Apsog 直到胚胎細胞化後，才被偵測到具有不對稱表現；由實驗結果推測胚胎背腹體軸形成從囊胚形成 (blastulation)開始，或是更早發生在多核囊胚 (syncytia) 時期，但已經不是依靠保守的背腹軸決定因子。

結果 (III) 生殖發育與內共生現象：初級內共生菌 Buchnera aphidicola 在原腸胚形成前就侵入蛋腔，在之後的所有胚胎發育時期一直此共生菌與生殖細胞緊密相鄰。基於觀察到此現象，我想要知道 B. aphidicola 是否為生殖細胞發育所必需。所以我藉由抗生素完全剔除蚜蟲體內的 B. aphidicola，發現這種缺共生菌的蚜蟲的生殖細胞數目會大量減少。因此我推測 B. aphidicola 提供的養分會影響生殖細胞增生。進一步藉由偵測到細胞凋亡因子 Caspase-3 會表現在缺共生蚜蟲的生殖細胞，顯示缺共生現象引起之生殖細胞數目減少是因為誘導生殖細胞發生凋亡 (apoptosis)。然而，生殖細胞移動路徑仍然不受抗生素處理之影響，此結果暗示誘導生殖細胞移動到性腺之因子不受到共生菌影響。

結論：本研究旨在透過探究發育工具組基因—Aphb、Apcad、 ApDl、Aphh、Apcact、Apdpp1–4、Apsog、mad 與 Apzen 等同源基因表現形式，藉以釐清孤雌胎生蚜蟲胚胎前後及背腹體軸建立之分子機制；此外，在體軸建立後，蚜蟲體內主要共生菌入侵胚胎進行共生，發現其對宿主胚胎發育過程中，調控生殖細胞存活之重要性，這些結果將有助於提供後續研究孤雌胎生昆蟲如何建立身體體制與其體內共生菌如何影響宿主胚胎與器官發育之參考。

Introduction. Aphids are hemipteran sap-sucking insects that can vector plant viruses. They propagate rapidly via parthenogenetic (asexual) and viviparous reproduction from generation to generation yet they enrich genetic diversity, once every life cycle, through sexual oviparous reproduction. In both asexual and sexual morphs, the primary endosymbiotic bacteria (endosymbionts) are critical to the synthesis of essential amino acids. With such special reproductive and endosymbiotic features described above, the pea aphid Acyrthosiphon pisum became a rising model insect after its whole genome sequence was published in 2010. Here in my study, I aimed to study two developmental events during early embryogenesis of the parthenogenetic and viviparous pea aphid: (1) the formation of anteroposterior (AP) and dorsoventral (DV) axes; and (2) the regulation of germline development by endosymbiosis.

Results (I) AP Axis Formation. Transcripts of Aphb, an ortholog of the Drosophila hunchback in the pea aphid, are known to be localized to the anterior poles of the oocytes and syncytia. This implies that anterior localization of Aphb mRNA may specify the anterior axis in the asexual viviparous pea aphid. In order to understand whether ApHb protein also participates in anterior formation via asymmetric localization as Aphb mRNA, dissected ovarioles were stained using an affinity-purified antibody against ApHb. I found that ApHb, unlike anteriorly-localized Aphb, was uniformly distributed in oocytes and syncytia. This suggests that ApHb is not involved in anterior formation. Both Aphb and ApHb, like their insect orthologs, were identified in the embryonic neuroblasts, indicating that the Aphb gene remained a conserved role in neurogenesis. Nevertheless, expression of Aphb and ApHb was unexpectedly detected in the germ cells throughout all developmental stages. Such germline expression pattern of hb has not been reported in other insect models, suggesting that Aphb may obtain a new role in germline development in asexual aphids. Transcripts of Apcad, an ortholog of the conserved posterior gene cad in the pea aphid, were not identified in the posterior region until blastoderm formation. The absence of posterior localization of Apcad mRNA in oocytes and syncytia suggests that Apcad, though remains conserved in posterior development, is not involved in posterior determination.

Results (II) DV Axis Formation. For studying how the DV axis was established, I detected expressions of orthologous mRNAs known to participate in the establishment of the DV axis in Drosophila, assuming that asymmetric localization of the target mRNAs was also conserved in the specification of DV axis in the asexual pea aphid. Transcripts of the four decapentaplegic paralogs (Apdpp1–4), however, unlike dorsal expression of dpp mRNA in Drosophila, was not particularly restricted to any regions within the egg chambers. I did not make antibodies against ApDpp1–4 proteins to detect their distributions. Nonetheless, signals of the phosphorylated Mothers Against Dpp (pMad) protein—a conserved indicator of Dpp activity—and those of Apzen (aphid zerknüllt (zen) ortholog) mRNA—a conserved marker for the insect extraembryonic membrane that forms from the dorsal region—were asymmetrically localized to one side within the egg chambers. Coincidentally, localization of Apsog mRNA, an orthologous mRNA of the ventral gene short gastrulation (sog) in Drosophila, was identified at the opposite side of pMad and zen expressions. The asymmetric localization of pMad/zen and Apsog was not detected until cellularization of the blastoderm, suggesting that formation of the DV axis stars from blastulation or it occurs earlier in the syncytia but does not rely on these conserved DV determinants.

Results (III) germline development and endosymbiosis. The primary endosymbiont Buchnera aphidicola invades into the egg chamber prior to gastrulation and ever since then it is associated with the embryonic germ cells throughout embryogenesis. Based upon the fact that the B. aphidicola and germ cells are closely associated, we aimed to understand whether B. aphidicola was essential to the development of germ cells. In the aposymbiotic pea aphids, where B. aphidicola was eliminated by antibiotics, the number of germ cells was largely reduced before katatrepsis (embryo flip), suggesting that B. aphidicola provides nutrients required for the proliferation of germ cells. Expression of Caspase-3 was identified in the germ cells of the aposymbiotic morphs, further suggesting that the reduction of germ cells is caused by apoptosis. The migratory path of germ cells, nevertheless, remained almost the same as that in aphids without the treatment of antibiotics. This implies that the delivery of the guiding signals for germline migration toward the gonads is independent from endosymbiosis.

Conclusion. In this study, the aphid orthologs of the developmental toolkit genes for the axis formation and body patterning, including Aphb, Apcad, ApDl, Aphh, Apcact, Apdpp1–4, Apsog, mad, and Apzen, were analyzed that allows to reveal how asexual viviparous aphid established body plan. After the formation of axes, Buchnera cells invade into the embryos that were required for regulating host germ-cell survival. Taken together, these results may shed light on how parthenogenetically viviparous insects established their body axes and how obligate symbionts of insects may play a non-nutritional role for host embryogenesis and organogenesis.

Contents
口試委員審定書………………………………………………………………. i
致謝……………………………………………………………………………. ii
摘要……………………………….….……….…….…………….…..……….. iii
Abstract….……………………………………………………………………. v
Contents……………………………………………………………………….. viii
Abbreviations…………………………………………………………………. xii
List of Tables………………………………………………………………….. xv
List of Figures……………………………………………..….……….…….… xvi
Chapter 1: General introduction…………………………………………….. 1
1.1. Basic biology of aphids: a brief review…………………………………….. 1
1.2. Biological features of the pea aphid Acyrthosiphon pisum……………..…. 1
1.3. The pea aphid is an emerging genetic model organism for Eco-Evo-Devo studies……………….…..............................................................................
2
1.4. The purpose of this study………………………………………………...... 4
Chapter 2: Materials and methods…………….………….…........….…...…. 5
2.1. Methodology for investigating the formation of body axes in the pea aphid.............................................................................................................
5
2.1.1. Aphid culture in Taiwan
2.1.2. Ovary culture, drug treatment, RNA extraction, and RT-PCR
2.1.3. Molecular cloning of developmental genes
2.1.4. Chromogenic in situ hybridization
2.1.5. Immunostaining
2.1.6. Photograph and image analysis
2.2. Methodology for investigating the interaction between Buchnera and germline development in the pea aphid……...………………….................
8
2.2.1. Aphid culture in Japan
2.2.2. Antibiotic treatment and artificial diets
2.2.3. Quantitative polymerase chain reaction for detecting bacterial DNA and germline mRNAs
2.2.4. Whole-mount in situ hybridization, immunostaining, and image analysis
2.2.5. Statistical analysis
2.3. Experimental procedure for establishing the platform to analyze the function of Apvas1 gene.……………...………….......................................
12
2.3.1. Design and synthesis of Apvas1 sgRNAs
2.3.2. Injection of CRISPR complex and mutation analysis
2.3.3. Mutation detection
Chapter 3: The body plan of the pea aphid………….……………………… 14
3.1. The origin of body axes in the insects........................................................... 14
3.1.1. Long-germ and short-germ developmental modes in insects
3.1.2. Embryogenesis of the pea aphid: a combination of long- and short-germ modes
3.1.3. The gene regulatory network of anteroposterior axis determination in long-germ insects: taking Drosophila as example
3.1.4. The machinery of anteroposterior patterning in Drosophila embryos: bcd and osk drive the AP patterning of embryos
3.2. The formation of anteroposterior axis in pea aphid……………….………. 18
3.2.1. Molecular network of AP axis in short-germ insects
3.2.2. The genetic network of gap genes regulates the formation of gnathic and thoracic segments in the short-germ insects
3.2.3. Gene periodicity of pair-rule genes trigger abdominal segmentation in short-germ insects
3.2.4. A conserved mechanism for the segment boundary formation and the segment identify in arthropods
3.3. The determination of dorsoventral axis in insects……….………………... 23
3.3.1. Setting up the dorsoventral axis in the Drosophila oocyte
3.3.2. The origin of DV patterning in the Drosophila embryo
3.3.3. The establishment of DV axis in the short-germ insects
3.4. Significances for studying body plan in the pea aphid……………….……. 27
3.5. Results……………………………………………………………………... 28
3.5.1. Identification of ApHb expression in the germ cells throughout aphid embryogenesis
3.5.2. Anterior localization of Aphb mRNA in oocytes and early embryos of the pea aphid via microtubule network
3.5.3. Noncanonical expression of Apcad gene in asexual and sexual oocytes and embryos
3.5.4 Expressions of the components in Hedgehog and Notch signaling pathways for the aphid segmentation
3.5.5. The localization of mRNA of cactus and dpp homologs was not required for specifying the dorsal region in viviparous embryos
3.5.6. Activating Dpp/BMP4 signaling specifies the dorsal-ventral axis of viviparous embryos
3.5.7. The dorsal specification and the formation of extraembryonic tissues in the pea aphid via activating zerknüllt gene
3.6. Discussions.……….….….….….….….….….……….….….….….….…... 37
3.6.1. Canonical and noncanonical expression of Aphb products in the pea aphid
3.6.2. Maternal-driven cad is not conserved in the posterior specification of the aphid embryo
3.6.3. Aphh, Apdelta, and Hox genes are highly conserved during germ-band elongation of the pea aphid
3.6.4. Dorsoventral patterning of the viviparous aphid embryos is not trigged by asymmetrical mRNA localization of Apdpp genes
Chapter 4: Interaction between obligate symbiont Buchnera aphidicola and host germline development………….……………………...
55
4.1. Background introduction of symbiosis and germline development in the asexual aphids………………………...…………………………….……...
55
4.2. Symbiosis influences on the reproductive capability in aphids…………… 55
4.3. The function of vasa homolog in animals………………………….…….... 56
4.4. Primary symbionts associate with primordial germ cells during germline migration……………………….….….….….….….….….………………..
57
4.5. Specific aims of this study………………………………………...….…… 58
4.6. Results……………………………………………………………………... 58
4.6.1. Aposymbiotic stress induced retardation of growth and became sterile in pea aphids
4.6.2. Aposymbiosis sparked off the downregulation of Apvas1 gene and reduction of germ-cell population
4.6.3. Expression of Apnos2, Appiwi2, and Aphb genes was dramatically decreased in PGCs after stage-12 development under aposymbiotic stress
4.6.4. Reduction of ApVas1 expression and Caspase-3 dependent apoptosis in primordial germ cells of aposymbiotic aphids
4.6.5. Reduction of apoptotic germ cells in aposymbiotic embryos after EAA compensation
4.7. Discussions……...………………………………….……........................... 65
4.7.1. Obligate symbiont Buchnera aphidicola is essential for the host development and germline development in pea aphids
4.7.2. The expression of Apvas1 in symbiotic regulation may play roles to prevent germline apoptosis under aposymbiotic stress
4.7.3. Extracellular signalings in symbiotic regulation may play roles to regulate expressions of germline genes
4.7.4. Obligate symbionts not only provide essential nutrients but also afford host a signal for reproduction
Chapter 5: The CRISPR genome-editing technology is a potential tool for analyzing developmental genes of aphids……………….………..
74
5.1. Background introduction………………………………………….……….. 74
5.2. Significant of this study…………………………………………….……… 75
5.3. Results……………………………………………………………………... 76
5.4. Discussions………...………………………….……………………...…… 79
5.4.1. The CRISPR/Cas9 system is a potential tool for analyzing developmental toolkit genes in the aphids
5.4.2. Lower hatching rate may cause by inbreeding depression
Chapter 6: Conclusion and epilogue…………………………………………. 83
References……………………………………………………………………... 86
List of appendix……………………………………………………………….. 182

References
Akam, M. (1987) The molecular basis for metameric pattern in the Drosophila embryo. Development 101: 1-22.
Akam, M., Averof, M., Castelli-Gair, J., Dawes, R., Falciani, F. and Ferrier, D. (1994) The evolving role of Hox genes in arthropods. Dev Suppl: 209-215.
Andreassi, C. and Riccio, A. (2009) To localize or not to localize: mRNA fate is in 3''-UTR ends. Trends Cell Biol 19: 465-474.
Arnosti, D.N., Barolo, S., Levine, M. and Small, S. (1996) The eve stripe 2 enhancer employs multiple modes of transcriptional synergy. Development 122: 205-214.
Ashe, H.L. and Levine, M. (1999) Local inhibition and long-range enhancement of Dpp signal transduction by Sog. Nature 398: 427-431.
Ballard, S.L., Jarolimova, J. and Wharton, K.A. (2010) Gbb/BMP signaling is required to maintain energy homeostasis in Drosophila. Dev Biol 337: 375-385.
Baonza, A. and Freeman, M. (2005) Control of cell proliferation in the Drosophila eye by Notch signaling. Dev Cell 8: 529-539.
Bassett, A.R., Tibbit, C., Ponting, C.P. and Liu, J.L. (2013) Highly efficient targeted mutagenesis of Drosophila with the CRISPR/Cas9 system. Cell Rep 4: 220-228.
Basturea, G.N., Zundel, M.A. and Deutscher, M.P. (2011) Degradation of ribosomal RNA during starvation: comparison to quality control during steady-state growth and a role for RNase PH. RNA 17: 338-345.
Baumann, P. (2005) Biology bacteriocyte-associated endosymbionts of plant sap-sucking insects. Annu Rev Microbiol 59: 155-189.
Belvin, M.P. and Anderson, K.V. (1996) A conserved signaling pathway: the Drosophila toll-dorsal pathway. Annu Rev Cell Dev Biol 12: 393-416.
Belvin, M.P., Jin, Y. and Anderson, K.V. (1995) Cactus protein degradation mediates Drosophila dorsal-ventral signaling. Genes Dev 9: 783-793.
Bergmann, A., Stein, D., Geisler, R., Hagenmaier, S., Schmid, B., Fernandez, N. et al. (1996) A gradient of cytoplasmic Cactus degradation establishes the nuclear localization gradient of the dorsal morphogen in Drosophila. Mech Dev 60: 109-123.
Berleth, T., Burri, M., Thoma, G., Bopp, D., Richstein, S., Frigerio, G. et al. (1988) The role of localization of bicoid RNA in organizing the anterior pattern of the Drosophila embryo. EMBO J 7: 1749-1756.
Beumer, K.J., Trautman, J.K., Bozas, A., Liu, J.L., Rutter, J., Gall, J.G. et al. (2008) Efficient gene targeting in Drosophila by direct embryo injection with zinc-finger nucleases. Proc Natl Acad Sci U S A 105: 19821-19826.
Blackman, R.L. (1978) Early development of parthenogenetic egg in three species of aphids (Homoptera Aphididae). Int J Insect Morphol 7: 33-44.
Bowers, W.S., Nault, L.R., Webb, R.E. and Dutky, S.R. (1972) Aphid alarm pheromone: isolation, identification, synthesis. Science 177: 1121-1122.
Brand, A.H. and Dormand, E.L. (1995) The GAL4 system as a tool for unravelling the mysteries of the Drosophila nervous system. Curr Opin Neurobiol 5: 572-578.
Brena, C. and Akam, M. (2013) An analysis of segmentation dynamics throughout embryogenesis in the centipede Strigamia maritima. BMC Biol 11: 112.
Brisson, J.A. and Stern, D.L. (2006) The pea aphid, Acyrthosiphon pisum: an emerging genomic model system for ecological, developmental and evolutionary studies. Bioessays 28: 747-755.
Buchner, P. (1965) Endosymbiosis of animals with plant microorganisms. Interscience Publishers, New York.
Buchta, T., Ozuak, O., Stappert, D., Roth, S. and Lynch, J.A. (2013) Patterning the dorsal-ventral axis of the wasp Nasonia vitripennis. Dev Biol 381: 189-202.
Caceres, L. and Nilson, L.A. (2005) Production of gurken in the nurse cells is sufficient for axis determination in the Drosophila oocyte. Development 132: 2345-2353.
Caillaud, M.C., Boutin, M., Braendle, C. and Simon, J.C. (2002) A sex-linked locus controls wing polymorphism in males of the pea aphid, Acyrthosiphon pisum (Harris). Heredity (Edinb) 89: 346-352.
Capecchi, M.R. (2005) Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nat Rev Genet 6: 507-512.
Carroll, S.B. and Scott, M.P. (1986) Zygotically active genes that affect the spatial expression of the fushi tarazu segmentation gene during early Drosophila embryogenesis. Cell 45: 113-126.
Cha, B.J., Koppetsch, B.S. and Theurkauf, W.E. (2001) In vivo analysis of Drosophila bicoid mRNA localization reveals a novel microtubule-dependent axis specification pathway. Cell 106: 35-46.
Chang, C.-c., Hsiao, Y.-m., Huang, T.Y., Cook, C.E., Shigenobu, S. and Chang, T.H. (2013) Noncanonical expression of caudal during early embryogenesis in the pea aphid Acyrthosiphon pisum: maternal cad-driven posterior development is not conserved. Insect Mol Biol 22: 442-455.
Chang, C.-c., Huang, T.Y., Shih, C.L., Lin, G.W., Chang, T.P., Chiu, H. et al. (2008) Whole-mount identification of gene transcripts in aphids: protocols and evaluation of probe accessibility. Arch Insect Biochem Physiol 68: 186-196.
Chang, C.-c., Dearden, P. and Akam, M. (2002) Germ line development in the grasshopper Schistocerca gregaria: vasa as a marker. Dev Biol 252: 100-118.
Chang, C.-c., Lee, W.C., Cook, C.E., Lin, G.W. and Chang, T. (2006) Germ-plasm specification and germline development in the parthenogenetic pea aphid Acyrthosiphon pisum: Vasa and Nanos as markers. Int J Dev Biol 50: 413-421.
Chang, C.-c., Lin, G.W., Cook, C.E., Horng, S.B., Lee, H.J. and Huang, T.Y. (2007) Apvasa marks germ-cell migration in the parthenogenetic pea aphid Acyrthosiphon pisum (Hemiptera: Aphidoidea). Dev Genes Evol 217: 275-287.
Charlesworth, D. and Willis, J.H. (2009) The genetics of inbreeding depression. Nat Rev Genet 10: 783-796.
Chen, G., Handel, K. and Roth, S. (2000) The maternal NF-kappaB/dorsal gradient of Tribolium castaneum: dynamics of early dorsoventral patterning in a short-germ beetle. Development 127: 5145-5156.
Cheptou, P.O. and Donohue, K. (2011) Environment-dependent inbreeding depression: its ecological and evolutionary significance. New Phytol 189: 395-407.
Chesebro, J.E., Pueyo, J.I. and Couso, J.P. (2013) Interplay between a Wnt-dependent organiser and the Notch segmentation clock regulates posterior development in Periplaneta americana. Biol Open 2: 227-237.
Christiaens, O., Swevers, L. and Smagghe, G. (2014) DsRNA degradation in the pea aphid (Acyrthosiphon pisum) associated with lack of response in RNAi feeding and injection assay. Peptides 53: 307-314.
Chung, C.Y., Cook, C.E., Lin, G.W., Huang, T.Y. and Chang, C.-c. (2014) Reliable protocols for whole-mount fluorescent in situ hybridization (FISH) in the pea aphid Acyrthosiphon pisum: a comprehensive survey and analysis. Insect Sci 21: 265-277.
Chung, C.Y., Hsiao, Y.-m., Huang, T.Y., Chang, T.H. and Chang, C.-c. (2018) Germline expression of the hunchback orthologues in the asexual viviparous aphids: a conserved feature within the Aphididae. Insect Mol Biol, in press.
Cong, L., Ran, F.A., Cox, D., Lin, S., Barretto, R., Habib, N., et al. (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339: 819-823.
Copf, T., Schröder, R. and Averof, M. (2004) Ancestral role of caudal genes in axis elongation and segmentation. Proc Natl Acad Sci U S A 101: 17711-17715.
Cox, D.N., Chao, A., Baker, J., Chang, L., Qiao, D. and Lin, H. (1998) A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev 12: 3715-3727.
Cruickshank, T. and Wade, M.J. (2008) Microevolutionary support for a developmental hourglass: gene expression patterns shape sequence variation and divergence in Drosophila. Evol Dev 10: 583-590.
Curtis, D., Lehmann, R. and Zamore, P.D. (1995) Translational regulation in development. Cell 81: 171-178.
Damen, W.G. (2007) Evolutionary conservation and divergence of the segmentation process in arthropods. Dev Dyn 236: 1379-1391.
Davis, G.K. (2012) Cyclical parthenogenesis and viviparity in aphids as evolutionary novelties. J Exp Zool B Mol Dev Evol 318: 448-459.
Davis, G.K. and Patel, N.H. (2002) Short, long, and beyond: molecular and embryological approaches to insect segmentation. Annu Rev Entomol 47: 669-699.
Dearden, P.K. and Akam, M. (2001) Early embryo patterning in the grasshopper, Schistocerca gregaria: wingless, decapentaplegic and caudal expression. Development 128: 3435-3444.
Dedeine, F., Vavre, F., Fleury, F., Loppin, B., Hochberg, M.E. and Bouletreau, M. (2001) Removing symbiotic Wolbachia bacteria specifically inhibits oogenesis in a parasitic wasp. Proc Natl Acad Sci U S A 98: 6247-6252.
Deshpande, G., Calhoun, G., Yanowitz, J.L. and Schedl, P.D. (1999) Novel functions of nanos in downregulating mitosis and transcription during the development of the Drosophila germline. Cell 99: 271-281.
Deshpande, G., Willis, E., Chatterjee, S., Fernandez, R., Dias, K. and Schedl, P. (2014) BMP signaling and the maintenance of primordial germ cell identity in Drosophila embryos. PLoS One 9: e88847.
Dixon, A.F.G. (1973) Metabolic acclimatization to seasonal changes in temperature in the sycamore aphid, Drepanosiphum platanoides (Schr.), and lime aphid, Eucallipterus tiliae L. Oecologia 13: 205-210.
Dixon, A.F.G. (1975) Seasonal changes in fat content, form, state of gonads and length of adult life in the sycamore aphid, Drepanosiphum platanoides (Schr.). Ecol. Entomol. 127: 87-99.
Dixson, A.F.G. (1977) Aphid Ecology: life cycles, polymorphism, and population regulation. Annu Rev Ecol Syst 8: 329-353.
Douglas, A.E. (1988) Experimental studies on the mycetome symbiosis in the leafhopper Euscelis incisus. J. Insect Physiol. 34: 1043-1053.
Douglas, A.E. (1993) The nutritional quality of phloem sap utilized by natural aphid populations. Ecol. Entomol. 18: 31-38.
Douglas, A.E. (1996) Reproductive failure and the free amino acid pools in pea aphids (Acyrthosiphon pisum) lacking symbiotic bacteria. J. Insect Physiol. 42: 9.
Douglas, A.E. (1998) Nutritional interactions in insect-microbial symbioses: aphids and their symbiotic bacteria Buchnera. Annu Rev Entomol 43: 17-37.
Douglas, A.E. (2000) Reproductive diapuse and the bacteriosymbiosis in the sycamore aphid Drepanosiphum platanoidis. Ecol. Entomol. 25: 256-261.
Douglas, A.E. and Prosser, W.A. (1992) Synthesis of the essential amino acid tryptophan in the pea aphid (Acyrthosiphon pisum) symbiosis. J. Insect Physiol. 38: 565-568.
Driever, W. and Nüsslein-Volhard, C. (1989) The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo. Nature 337: 138-143.
Duboule, D. (1994) Temporal colinearity and the phylotypic progression: a basis for the stability of a vertebrate Bauplan and the evolution of morphologies through heterochrony. Dev Suppl: 135-142.
Duncan, E.J., Leask, M.P. and Dearden, P.K. (2013) The pea aphid (Acyrthosiphon pisum) genome encodes two divergent early developmental programs. Dev Biol 377: 262-274.
Eeken, J.C., de Jong, A.W., Loos, M., Vreeken, C., Romeyn, R., Pastink, A. et al. (1994) The nature of X-ray-induced mutations in mature sperm and spermatogonial cells of Drosophila melanogaster. Mutat Res 307: 201-212.
Eisler, H., Frohlich, K.U. and Heidenreich, E. (2004) Starvation for an essential amino acid induces apoptosis and oxidative stress in yeast. Exp Cell Res 300: 345-353.
Engels, W.R. (1992) The origin of P elements in Drosophila melanogaster. Bioessays 14: 681-686.
Ephrussi, A. and Lehmann, R. (1992) Induction of germ cell formation by oskar. Nature 358: 387-392.
Ewen-Campen, B., Jones, T.E. and Extavour, C.G. (2013) Evidence against a germ plasm in the milkweed bug Oncopeltus fasciatus, a hemimetabolous insect. Biol Open 2: 556-68.
Ewen-Campen, B., Srouji, J.R., Schwager, E.E. and Extavour, C.G. (2012) Oskar predates the evolution of germ plasm in insects. Curr Biol 22: 2278-2283.
Extavour, C.G. (2011) Long-lost relative claims orphan gene: oskar in a wasp. PLoS Genet 7: e1002045.
Falciani, F., Hausdorf, B., Schröder, R., Akam, M., Tautz, D., Denell, R. et al. (1996) Class 3 Hox genes in insects and the origin of zen. Proc Natl Acad Sci U S A 93: 8479-8484.
Farzana, L. and Brown, S.J. (2008) Hedgehog signaling pathway function conserved in Tribolium segmentation. Dev Genes Evol 218: 181-192.
Ferguson, E.L. and Anderson, K.V. (1992a) Decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo. Cell 71: 451-461.
Ferguson, E.L. and Anderson, K.V. (1992b) Localized enhancement and repression of the activity of the TGF-beta family member, decapentaplegic, is necessary for dorsal-ventral pattern formation in the Drosophila embryo. Development 114: 583-597.
Forbes, A. and Lehmann, R. (1998) Nanos and Pumilio have critical roles in the development and function of Drosophila germline stem cells. Development 125: 679-690.
Francois, V., Solloway, M., O''Neill, J.W., Emery, J. and Bier, E. (1994) Dorsal-ventral patterning of the Drosophila embryo depends on a putative negative growth factor encoded by the short gastrulation gene. Genes Dev 8: 2602-2616.
Franek, F., Fismolova, I. and Eckschlager, T. (2002) Antiapoptotic and proapoptotic action of various amino acids and analogs in starving MOLT-4 cells. Arch Biochem Biophys 398: 141-146.
Fujioka, M., Emi-Sarker, Y., Yusibova, G.L., Goto, T. and Jaynes, J.B. (1999) Analysis of an even-skipped rescue transgene reveals both composite and discrete neuronal and early blastoderm enhancers, and multi-stripe positioning by gap gene repressor gradients. Development 126: 2527-2538.
Fujiwara, Y., Komiya, T., Kawabata, H., Sato, M., Fujimoto, H., Furusawa, M. et al. (1994) Isolation of a DEAD-family protein gene that encodes a murine homolog of Drosophila vasa and its specific expression in germ cell lineage. Proc Natl Acad Sci U S A 91: 12258-12262.
Fukatsu, T. and Ishikawa, H. (1992) Soldier and male of an eusocial aphid Colophina arma lack endosymbiont: Implications for physiological and evolutionary interaction between host and symbiont. J. Insect Physiol. 38: 1033-1042.
Gaj, T., Gersbach, C.A. and Barbas, C.F. (2013) ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 31: 397-405.
Gavis, E.R., Lunsford, L., Bergsten, S.E. and Lehmann, R. (1996) A conserved 90 nucleotide element mediates translational repression of nanos RNA. Development 122: 2791-2800.
Gilbert, S.F. (2014) Developmental Symbiosis. In: Developmental Biology. pp. 680-684. Sinauer Associates, Inc. , Sunderland.
Gilbert, S.F., McDonald, E., Boyle, N.; Buttino, N., Gyi, L., Mai, M. et al. (2010) Symbiosis as a source of selectable epigenetic variation: taking the heat for the big guy. Phil. Trans. R. Soc. B 365: 671-678.
Golic, K.G. (1991) Site-specific recombination between homologous chromosomes in Drosophila. Science 252: 958-961.
Goltsev, Y., Fuse, N., Frasch, M., Zinzen, R.P., Lanzaro, G. and Levine, M. (2007) Evolution of the dorsal-ventral patterning network in the mosquito, Anopheles gambiae. Development 134: 2415-2424.
González-Reyes, A., Elliott, H. and St Johnston, D. (1995) Polarization of both major body axes in Drosophila by gurken-torpedo signalling. Nature 375: 654-658.
Grandison, R.C., Piper, M.D. and Partridge, L. (2009) Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462: 1061-1064.
Gratz, S.J., Cummings, A.M., Nguyen, J.N., Hamm, D.C., Donohue, L.K., Harrison, M.M. et al. (2013) Genome engineering of Drosophila with the CRISPR RNA-guided Cas9 nuclease. Genetics 194: 1029-1035.
Gray, S. and Levine, M. (1996) Transcriptional repression in development. Curr Opin Cell Biol 8: 358-364.
Green, J. and Akam, M. (2013) Evolution of the pair rule gene network: Insights from a centipede. Dev Biol 382: 235-245.
Gupta, R.M. and Musunuru, K. (2014) Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. J Clin Invest 124: 4154-4161.
Haines, J.W., Coster, M. and Bouffler, S.D. (2015) Impairment of the non-homologous end joining and homologous recombination pathways of DNA double strand break repair: Impact on spontaneous and radiation-induced mammary and intestinal tumour risk in Apc min/+ mice. DNA Repair (Amst) 35: 19-26.
Hansen, A.K. and Moran, N.A. (2011) Aphid genome expression reveals host-symbiont cooperation in the production of amino acids. Proc Natl Acad Sci U S A 108: 2849-2854.
Hansen, M., Flatt, T. and Aguilaniu, H. (2013) Reproduction, fat metabolism, and life span: what is the connection? Cell Metab 17: 10-19.
Hanyu-Nakamura, K., Kobayashi, S. and Nakamura, A. (2004) Germ cell-autonomous Wunen2 is required for germline development in Drosophila embryos. Development 131: 4545-4553.
Hartung, O., Forbes, M.M. and Marlow, F.L. (2014) Zebrafish vasa is required for germ-cell differentiation and maintenance. Mol Reprod Dev 81: 946-961.
Hay, B., Ackerman, L., Barbel, S., Jan, L.Y. and Jan, Y.N. (1988) Identification of a component of Drosophila polar granules. Development 103: 625-640.
Hayashi, Y., Hayashi, M. and Kobayashi, S. (2004) Nanos suppresses somatic cell fate in Drosophila germ line. Proc Natl Acad Sci U S A 101: 10338-10342.
Hertig, M. and Wolbach, S. B. (1924) Studies on rickettsia-like microorganisms in insects. J. Med. Res. 44: 329-374.7.
Hidalgo, A. and Ingham, P. (1990) Cell patterning in the Drosophila segment: spatial regulation of the segment polarity gene patched. Development 110: 291-301.
Hilbrant, M., Horn, T., Koelzer, S. and Panfilio, K.A. (2016) The beetle amnion and serosa functionally interact as apposed epithelia. Elife 5: e13834.
Holley, S.A., Jackson, P.D., Sasai, Y., Lu, B., De Robertis, E.M., Hoffmann, F.M. et al. (1995) A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin. Nature 376: 249-253.
Holliday, R. (1989) Food, reproduction and longevity: is the extended lifespan of calorie-restricted animals an evolutionary adaptation? Bioessays 10: 125-127.
Hong, J.W., Hendrix, D.A., Papatsenko, D. and Levine, M.S. (2008) How the Dorsal gradient works: insights from postgenome technologies. Proc Natl Acad Sci U S A 105: 20072-20076.
Hosokawa, T., Koga, R., Kikuchi, Y., Meng, X.Y. and Fukatsu, T. (2010) Wolbachia as a bacteriocyte-associated nutritional mutualist. Proc Natl Acad Sci U S A 107: 769-774.
Houwing, S., Kamminga, L.M., Berezikov, E., Cronembold, D., Girard, A., van den Elst, H. et al. (2007) A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish. Cell 129: 69-82.
Hughes, C.L., Liu, P.Z. and Kaufman, T.C. (2004) Expression patterns of the rogue Hox genes Hox3/zen and fushi tarazu in the apterygote insect Thermobia domestica. Evol Dev 6: 393-401.
Hsiao, Y.-m., Lin, G.W. and Chang, C.-c. (2014) Establishment of the pea aphid as a developmental model organism: history, significance, and future prospects. Formosan Entomol. 33: 215-235.
Hsu, P.D., Lander, E.S. and Zhang, F. (2014) Development and applications of CRISPR-Cas9 for genome engineering. Cell 157: 1262-1278.
Huang, M.H. and Caillaud, M.C. (2012) Inbreeding avoidance by recognition of close kin in the pea aphid, Acyrthosiphon pisum. J Insect Sci 12: 39.
Huang, T.Y., Cook, C.E., Davis, G.K., Shigenobu, S., Chen, R.P. and Chang, C.-c. (2010) Anterior development in the parthenogenetic and viviparous form of the pea aphid, Acyrthosiphon pisum: hunchback and orthodenticle expression. Insect Mol Biol 19 Suppl 2: 75-85.
Ingham, P.W., Nakano, Y. and Seger, C. (2011) Mechanisms and functions of Hedgehog signalling across the metazoa. Nat Rev Genet 12: 393-406.
Irish, V., Lehmann, R. and Akam, M. (1989) The Drosophila posterior-group gene nanos functions by repressing hunchback activity. Nature 338: 646-648.
Ishikawa, A., Ogawa, K., Gotoh, H., Walsh, T.K., Tagu, D., Brisson, J.A., et al. (2012) Juvenile hormone titre and related gene expression during the change of reproductive modes in the pea aphid. Insect Mol Biol 21: 49-60.
Izawa, T., Ogasawara, J., Sakurai, T., Nomura, S., Kizaki, T. and Ohno, H. (2012) Recent advances in the adaptations of adipose tissue to physical activity: Morphology and adipose tissue cellularity. J Phys Fitness Sports Med 1: 381-387.
Jaeger, J. (2011) The gap gene network. Cell Mol Life Sci 68: 243-274.
Jambor, H., Mueller, S., Bullock, S.L. and Ephrussi, A. (2014) A stem-loop structure directs oskar mRNA to microtubule minus ends. RNA 20: 429-439.
Jaubert-Possamai, S., Le Trionnaire, G., Bonhomme, J., Christophides, G.K., Rispe, C. and Tagu, D. (2007) Gene knockdown by RNAi in the pea aphid Acyrthosiphon pisum. BMC Biotechnol 7: 63.
Jiang, Y.J., Aerne, B.L., Smithers, L., Haddon, C., Ish-Horowicz, D. and Lewis, J. (2000) Notch signalling and the synchronization of the somite segmentation clock. Nature 408: 475-479.
Kalinka, A.T., Varga, K.M., Gerrard, D.T., Preibisch, S., Corcoran, D.L., Jarrells, J., et al. (2010) Gene expression divergence recapitulates the developmental hourglass model. Nature 468: 811-814.
Kanayama, M., Akiyama-Oda, Y., Nishimura, O., Tarui, H., Agata, K. and Oda, H. (2011) Travelling and splitting of a wave of hedgehog expression involved in spider-head segmentation. Nat Commun 2: 500.
Kanodia, J.S., Rikhy, R., Kim, Y., Lund, V.K., DeLotto, R., Lippincott-Schwartz, J. et al. (2009) Dynamics of the Dorsal morphogen gradient. Proc Natl Acad Sci U S A 106: 21707-21712.
Katsuyama, T., Akmammedov, A., Seimiya, M., Hess, S.C., Sievers, C. and Paro, R. (2013) An efficient strategy for TALEN-mediated genome engineering in Drosophila. Nucleic Acids Res 41: e163.
Kephart, S.R., Brown, E. and Hall, J. (1999) Inbreeding depression and partial selfing: evolutionary implications of mixed-mating in a coastal endemic, silene douglasii var. oraria (Caryophyllaceae). Heredity (Edinb) 82 (Pt 5): 543-554.
Kim, J., Johnson, K., Chen, H.J., Carroll, S. and Laughon, A. (1997) Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Nature 388: 304-308.
Kirkwood, T.B. (1977) Evolution of ageing. Nature 270: 301-304.
Kobayashi, S., Yamada, M., Asaoka, M. and Kitamura, T. (1996) Essential role of the posterior morphogen nanos for germline development in Drosophila. Nature 380: 708-711.
Koga, R., Tsuchida, T. and Fukatsu, T. (2003) Changing partners in an obligate symbiosis: a facultative endosymbiont can compensate for loss of the essential endosymbiont Buchnera in an aphid. Proc Biol Sci 270: 2543-2550.
Kotkamp, K., Klingler, M. and Schoppmeier, M. (2010) Apparent role of Tribolium orthodenticle in anteroposterior blastoderm patterning largely reflects novel functions in dorsoventral axis formation and cell survival. Development 137: 1853-1862.
Kugler, J.M. and Lasko, P. (2009) Localization, anchoring and translational control of oskar, gurken, bicoid and nanos mRNA during Drosophila oogenesis. Fly (Austin) 3: 15-28.
Kunwar, P.S., Siekhaus, D.E. and Lehmann, R. (2006) In vivo migration: a germ cell perspective. Annu Rev Cell Dev Biol 22: 237-265.
Kunwar, P.S., Starz-Gaiano, M., Bainton, R.J., Heberlein, U. and Lehmann, R. (2003) Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells. PLoS Biol 1: E80.
Kwan, C.W., Gavin-Smyth, J., Ferguson, E.L. and Schmidt-Ott, U. (2016) Functional evolution of a morphogenetic gradient. Elife 5: e20894.
Landmann, F.F., J. M.; Michalski, M. L.; Slatko, B. E.; Sullivan, W. (2014) Coevolution between an endosymbiont and its nematode host: Wolbachia asymmetric posterior localization and AP polarity establishment. PLoS Negl Trop Dis 8: e3096.
Lasko, P. (1999) RNA sorting in Drosophila oocytes and embryos. FASEB J 13: 421-433.
Lasko, P.F. and Ashburner, M. (1988) The product of the Drosophila gene vasa is very similar to eukaryotic initiation factor-4A. Nature 335: 611-617.
Le Trionnaire, G., Hardie, J., Jaubert-Possamai, S., Simon, J.C. and Tagu, D. (2008) Shifting from clonal to sexual reproduction in aphids: physiological and developmental aspects. Biol Cell 100: 441-451.
Lecuit, T., Brook, W.J., Ng, M., Calleja, M., Sun, H. and Cohen, S.M. (1996) Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing. Nature 381: 387-393.
Leptin, M. (1995) Drosophila gastrulation: from pattern formation to morphogenesis. Annu Rev Cell Dev Biol 11: 189-212.
Leu, S.-J.C., Li, K.-K.J. and Hsiao, T.H. (1989) Characterization of Wolbachia postica, the cause of reproductive incompatibility among alfalfa weevil strains. J. Invertebr. Pathol. 54: 12.
Lewis, E.B. (1978) A gene complex controlling segmentation in Drosophila. Nature 276: 565-570.
Li, L., Atef, A., Piatek, A., Ali, Z., Piatek, M., Aouida, M. et al. (2013) Characterization and DNA-binding specificities of Ralstonia TAL-like effectors. Mol Plant 6: 1318-1330.
Liang, L., Diehl-Jones, W. and Lasko, P. (1994) Localization of vasa protein to the Drosophila pole plasm is independent of its RNA-binding and helicase activities. Development 120: 1201-1211.
Liao, B.K. and Oates, A.C. (2017) Delta-Notch signalling in segmentation. Arthropod Struct Dev 46: 429-447.
Liberman, L.M., Reeves, G.T. and Stathopoulos, A. (2009) Quantitative imaging of the Dorsal nuclear gradient reveals limitations to threshold-dependent patterning in Drosophila. Proc Natl Acad Sci U S A 106: 22317-22322.
Lin, G.W. and Chang, C.-c. (2016) Identification of critical conditions for immunostaining in the pea aphid embryos: increasing tissue permeability and decreasing background dtaining. J Vis Exp (108): e53883.
Lin, G.W., Cook, C.E., Miura, T. and Chang, C.-c. (2014) Posterior localization of ApVas1 positions the preformed germ plasm in the sexual oviparous pea aphid Acyrthosiphon pisum. Evodevo 5: 18.
Liu, P.Z. and Kaufman, T.C. (2004) hunchback is required for suppression of abdominal identity, and for proper germband growth and segmentation in the intermediate germband insect Oncopeltus fasciatus. Development 131: 1515-1527.
Liu, P.Z. and Kaufman, T.C. (2005) Short and long germ segmentation: unanswered questions in the evolution of a developmental mode. Evol Dev 7: 629-646.
Livak, K.J. and Schmittgen, T.D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402-408.
Lu, H.L., Tanguy, S., Rispe, C., Gauthier, J.P., Walsh, T., Gordon, K., et al. (2011) Expansion of genes encoding piRNA-associated argonaute proteins in the pea aphid: diversification of expression profiles in different plastic morphs. PLoS One 6: e28051.
Lynch, J.A., Brent, A.E., Leaf, D.S., Pultz, M.A. and Desplan, C. (2006) Localized maternal orthodenticle patterns anterior and posterior in the long germ wasp Nasonia. Nature 439: 728-732.
Lynch, J.A. and Desplan, C. (2010) Novel modes of localization and function of nanos in the wasp Nasonia. Development 137: 3813-3821.
Lynch, J.A., El-Sherif, E. and Brown, S.J. (2012) Comparisons of the embryonic development of Drosophila , Nasonia , and Tribolium. WIREs Dev Biol 1: 16-39.
Lynch, J.A. and Roth, S. (2011) The evolution of dorsal-ventral patterning mechanisms in insects. Genes Dev 25: 107-118.
Ma, D. and Liu, F. (2015) Genome editing and its applications in model organisms. Genom Proteom Bioinf 13: 336-344.
Macdonald, P.M. and Smibert, C.A. (1996) Translational regulation of maternal mRNAs. Curr Opin Genet Dev 6: 403-407.
Mahfouz, M.M., Piatek, A. and Stewart, C.N., Jr. (2014) Genome engineering via TALENs and CRISPR/Cas9 systems: challenges and perspectives. Plant Biotechnol J 12: 1006-1014.
Mahmoud, J., Fossett, N.G., Arbour-Reily, P., McDaniel, M., Tucker, A., Chang, S.H. et al. (1991) DNA sequence analysis of X-ray induced Adh null mutations in Drosophila melanogaster. Environ Mol Mutagen 18: 157-160.
Martin, A., Serano, J.M., Jarvis, E., Bruce, H.S., Wang, J., Ray, S., et al. (2016) CRISPR/Cas9 mutagenesis reveals versatile roles of Hox genes in crustacean limb specification and evolution. Curr Biol 26: 14-26.
McGregor, A.P., Pechmann, M., Schwager, E.E. and Damen, W.G. (2009) An ancestral regulatory network for posterior development in arthropods. Commun Integr Biol 2: 174-176.
Medzhitov, R., Preston-Hurlburt, P. and Janeway, C.A., Jr. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388: 394-397.
Michaelson, D., Korta, D.Z., Capua, Y. and Hubbard, E.J. (2010) Insulin signaling promotes germline proliferation in C. elegans. Development 137: 671-680.
Mische, S., Li, M., Serr, M. and Hays, T.S. (2007) Direct observation of regulated ribonucleoprotein transport across the nurse cell/oocyte boundary. Mol Biol Cell 18: 2254-2263.
Mito, T., Kobayashi, C., Sarashina, I., Zhang, H., Shinahara, W., Miyawaki, K., et al. (2007) even-skipped has gap-like, pair-rule-like, and segmental functions in the cricket Gryllus bimaculatus, a basal, intermediate germ insect (Orthoptera). Dev Biol 303: 202-213.
Mito, T., Nakamura, T. and Noji, S. (2010) Evolution of insect development: to the hemimetabolous paradigm. Curr Opin Genet Dev 20: 355-361.
Mito, T., Okamoto, H., Shinahara, W., Shinmyo, Y., Miyawaki, K., Ohuchi, H. et al. (2006) Krüppel acts as a gap gene regulating expression of hunchback and even-skipped in the intermediate germ cricket Gryllus bimaculatus. Dev Biol 294: 471-481.
Mito, T., Sarashina, I., Zhang, H., Iwahashi, A., Okamoto, H., Miyawaki, K., et al. (2005) Non-canonical functions of hunchback in segment patterning of the intermediate germ cricket Gryllus bimaculatus. Development 132: 2069-2079.
Mito, T., Shinmyo, Y., Kurita, K., Nakamura, T., Ohuchi, H. and Noji, S. (2011) Ancestral functions of Delta/Notch signaling in the formation of body and leg segments in the cricket Gryllus bimaculatus. Development 138: 3823-3833.
Miura, T., Braendle, C., Shingleton, A., Sisk, G., Kambhampati, S. and Stern, D.L. (2003) A comparison of parthenogenetic and sexual embryogenesis of the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidoidea). J Exp Zool B Mol Dev Evol 295: 59-81.
Miyawaki, K., Mito, T., Sarashina, I., Zhang, H., Shinmyo, Y., Ohuchi, H. et al. (2004) Involvement of Wingless/Armadillo signaling in the posterior sequential segmentation in the cricket, Gryllus bimaculatus (Orthoptera), as revealed by RNAi analysis. Mech Dev 121: 119-130.
Mlodzik, M. and Gehring, W.J. (1987) Expression of the caudal gene in the germ line of Drosophila: formation of an RNA and protein gradient during early embryogenesis. Cell 48: 465-478.
Montllor, C.B., Maxman, A. and Purcell, A.H. (2002) Facultative bacterial endosymbionts benefit pea aphids Acyrthosiphon pisum under heat stress. Ecol Entomol 27: 189-195.
Morisato, D. and Anderson, K.V. (1995) Signaling pathways that establish the dorsal-ventral pattern of the Drosophila embryo. Annu Rev Genet 29: 371-399.
Moussian, B. and Roth, S. (2005) Dorsoventral axis formation in the Drosophila embryo--shaping and transducing a morphogen gradient. Curr Biol 15: R887-R899.
Muller, H.J. (1927) Artificial Transmutation of the gene. Science 66: 84-87.
Mutti, N.S., Louis, J., Pappan, L.K., Pappan, K., Begum, K., Chen, M.S., et al. (2008) A protein from the salivary glands of the pea aphid, Acyrthosiphon pisum, is essential in feeding on a host plant. Proc Natl Acad Sci U S A 105: 9965-9969.
Mutti, N.S., Park, Y., Reese, J.C. and Reeck, G.R. (2006) RNAi knockdown of a salivary transcript leading to lethality in the pea aphid, Acyrthosiphon pisum. J Insect Sci 6: 1-7.
Naito, Y., Hino, K., Bono, H. and Ui-Tei, K. (2015) CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites. Bioinformatics 31: 1120-1123.
Nemudryi, A.A., Valetdinova, K.R., Medvedev, S.P. and Zakian, S.M. (2014) TALEN and CRISPR/Cas genome editing systems: tools of discovery. Acta Naturae 6: 19-40.
Noda, H. (1984) Cytoplasmic incompatibility in allopatric field populations of the small brown planthopper, Laodelphax striatellus, in Japan. Entomol Exp Appl 35: 4.
Nüsslein-Volhard, C., Frohnhofer, H.G. and Lehmann, R. (1987) Determination of anteroposterior polarity in Drosophila. Science 238: 1675-1681.
Nunes da Fonseca, R., von Levetzow, C., Kalscheuer, P., Basal, A., van der Zee, M. and Roth, S. (2008) Self-regulatory circuits in dorsoventral axis formation of the short-germ beetle Tribolium castaneum. Dev Cell 14: 605-615.
O''Connell, M.D. and Reeves, G.T. (2015) The presence of nuclear cactus in the early Drosophila embryo may extend the dynamic range of the dorsal gradient. PLoS Comput Biol 11: e1004159.
Ogawa, K. and Miura, T. (2013) Two developmental switch points for the wing polymorphisms in the pea aphid Acyrthosiphon pisum. Evodevo 4: 30.
Ohnishi, O. (1977) Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. III. Heterozygous effect of polygenic mutations. Genetics 87: 547-556.
Olesnicky, E.C., Brent, A.E., Tonnes, L., Walker, M., Pultz, M.A., Leaf, D. et al. (2006) A caudal mRNA gradient controls posterior development in the wasp Nasonia. Development 133: 3973-3982.
Olesnicky, E.C. and Desplan, C. (2007) Distinct mechanisms for mRNA localization during embryonic axis specification in the wasp Nasonia. Dev Biol 306: 134-142.
Ortiz-Rivas, B. and Martinez-Torres, D. (2010) Combination of molecular data support the existence of three main lineages in the phylogeny of aphids (Hemiptera: Aphididae) and the basal position of the subfamily Lachninae. Mol Phylogenet Evol 55: 305-317.
Özhan-Kizil, G., Havemann, J. and Gerberding, M. (2009) Germ cells in the crustacean Parhyale hawaiensis depend on Vasa protein for their maintenance but not for their formation. Dev Biol 327: 230-239.
Panfilio, K.A. (2008) Extraembryonic development in insects and the acrobatics of blastokinesis. Dev Biol 313: 471-491.
Panfilio, K.A. (2009) Late extraembryonic morphogenesis and its zen(RNAi)-induced failure in the milkweed bug Oncopeltus fasciatus. Dev Biol 333: 297-311.
Panfilio, K.A., Liu, P.Z., Akam, M. and Kaufman, T.C. (2006) Oncopeltus fasciatus zen is essential for serosal tissue function in katatrepsis. Dev Biol 292: 226-243.
Pannebakker, B.A., Loppin, B., Elemans, C.P., Humblot, L. and Vavre, F. (2007) Parasitic inhibition of cell death facilitates symbiosis. Proc Natl Acad Sci U S A 104: 213-215.
Patel, N.H., Hayward, D.C., Lall, S., Pirkl, N.R., DiPietro, D. and Ball, E.E. (2001) Grasshopper hunchback expression reveals conserved and novel aspects of axis formation and segmentation. Development 128: 3459-3472.
Peel, A. (2004) The evolution of arthropod segmentation mechanisms. Bioessays 26: 1108-1116.
Peel, A.D., Chipman, A.D. and Akam, M. (2005) Arthropod segmentation: beyond the Drosophila paradigm. Nat Rev Genet 6: 905-916.
Pinnell, J., Lindeman, P.S., Colavito, S., Lowe, C. and Savage, R.M. (2006) The divergent roles of the segmentation gene hunchback. Integr Comp Biol 46: 519-532.
Pitino, M., Coleman, A.D., Maffei, M.E., Ridout, C.J. and Hogenhout, S.A. (2011) Silencing of aphid genes by dsRNA feeding from plants. PLoS One 6: e25709.
Pitino, M. and Hogenhout, S.A. (2013) Aphid protein effectors promote aphid colonization in a plant species-specific manner. Mol Plant Microbe Interact 26: 130-139.
Pueyo, J.I., Lanfear, R. and Couso, J.P. (2008) Ancestral Notch-mediated segmentation revealed in the cockroach Periplaneta americana. Proc Natl Acad Sci U S A 105: 16614-16619.
Pusey, A.E. (1987) Sex-biased dispersal and inbreeding avoidance in birds and mammals. Trends Ecol Evol 2: 295-299.
Pultz, M.A., Westendorf, L., Gale, S.D., Hawkins, K., Lynch, J., Pitt, J.N. et al. (2005) A major role for zygotic hunchback in patterning the Nasonia embryo. Development 132: 3705-3715.
Qian, S.W., Tang, Y., Li, X., Liu, Y., Zhang, Y.Y., Huang, H.Y. et al. (2013) BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis. Proc Natl Acad Sci U S A 110: E798-E807.
Raff, R.A. (1996) The Shape of Life: Genes, Development, and the Evolution. John Wiley and Sons, New York.
Rafiqi, A.M., Lemke, S., Ferguson, S., Stauber, M. and Schmidt-Ott, U. (2008) Evolutionary origin of the amnioserosa in cyclorrhaphan flies correlates with spatial and temporal expression changes of zen. Proc Natl Acad Sci U S A 105: 234-239.
Rafiqi, A.M., Park, C.H., Kwan, C.W., Lemke, S. and Schmidt-Ott, U. (2012) BMP-dependent serosa and amnion specification in the scuttle fly Megaselia abdita. Development 139: 3373-3382.
Ran, F.A., Hsu, P.D., Lin, C.Y., Gootenberg, J.S., Konermann, S., Trevino, A.E. et al. (2013) Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 154: 1380-1389.
Rauskolb, C. and Irvine, K.D. (1999) Notch-mediated segmentation and growth control of the Drosophila leg. Dev Biol 210: 339-350.
Raz, E. (2004) Guidance of primordial germ cell migration. Curr Opin Cell Biol 16: 169-173.
Reach, M., Galindo, R.L., Towb, P., Allen, J.L., Karin, M. and Wasserman, S.A. (1996) A gradient of cactus protein degradation establishes dorsoventral polarity in the Drosophila embryo. Dev Biol 180: 353-364.
Richardson, B.E. and Lehmann, R. (2010) Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat Rev Mol Cell Biol 11: 37-49.
Rivera-Pomar, R., Niessing, D., Schmidt-Ott, U., Gehring, W.J. and Jäckle, H. (1996) RNA binding and translational suppression by bicoid. Nature 379: 746-749.
Rong, Y.S. and Golic, K.G. (2000) Gene targeting by homologous recombination in Drosophila. Science 288: 2013-2018.
Rongo, C., Gavis, E.R. and Lehmann, R. (1995) Localization of oskar RNA regulates oskar translation and requires Oskar protein. Development 121: 2737-2746.
Roth, S., Hiromi, Y., Godt, D. and Nüsslein-Volhard, C. (1991) cactus, a maternal gene required for proper formation of the dorsoventral morphogen gradient in Drosophila embryos. Development 112: 371-388.
Roth, S. and Panfilio, K.A. (2012) Development. Making waves for segments. Science 336: 306-307.
Roth, S. and Schupbach, T. (1994) The relationship between ovarian and embryonic dorsoventral patterning in Drosophila. Development 120: 2245-2257.
Rushlow, C. and Levine, M. (1990) Role of the zerknüllt gene in dorsal-ventral pattern formation in Drosophila. Adv Genet 27: 277-307.
Russell, J.J., Theriot, J.A., Sood, P., Marshall, W.F., Landweber, L.F., Fritz-Laylin, L., et al. (2017) Non-model model organisms. BMC Biol 15: 55.
Sabeter-Muñoz, B., van Ham, R.C.H.J., MartÍnez-Torres, D., Silva, F.J., . Latorre, A. and Moya, A. (2001) Molecular-evolution of aphids and their primary (Buchnera sp.) and secondary endosymbionts: implications for the role of symbiosis in insect evolution. Interciencia 26: 508-512.
Sachs, L., Chen, Y.T., Drechsler, A., Lynch, J.A., Panfilio, K.A., Lassig, M. et al., (2015) Dynamic BMP signaling polarized by Toll patterns the dorsoventral axis in a hemimetabolous insect. Elife 4: e05502
Sadowski, P.D. (1995) The Flp recombinase of the 2-microns plasmid of Saccharomyces cerevisiae. Prog Nucleic Acid Res Mol Biol 51: 53-91.
Sakagami, H., Satoh, M., Yokote, Y., Takano, H., Takahama, M., Kochi, M. et al. (1998) Amino acid utilization during cell growth and apoptosis induction. Anticancer Res 18: 4303-4306.
Sanchez-Herrero, E., Vernos, I., Marco, R. and Morata, G. (1985) Genetic organization of Drosophila bithorax complex. Nature 313: 108-113.
Sander, K. (1976) Specification of the basic body pattern in insect embryogenesis. Adv. In Insect Phys. 12: 125-238.
Sanson, B. (2001) Generating patterns from fields of cells. Examples from Drosophila segmentation. EMBO Rep 2: 1083-1088.
Sanson, B., Alexandre, C., Fascetti, N. and Vincent, J.P. (1999) Engrailed and hedgehog make the range of Wingless asymmetric in Drosophila embryos. Cell 98: 207-216.
Santos, A.C. and Lehmann, R. (2004) Germ cell specification and migration in Drosophila and beyond. Curr Biol 14: R578-R589.
Sapountzis, P., Duport, G., Balmand, S., Gaget, K., Jaubert-Possamai, S., Febvay, G. et al. (2014) New insight into the RNA interference response against cathepsin-L gene in the pea aphid, Acyrthosiphon pisum: molting or gut phenotypes specifically induced by injection or feeding treatments. Insect Biochem Mol Biol 51: 20-32.
Sarrazin, A.F., Peel, A.D. and Averof, M. (2012) A segmentation clock with two-segment periodicity in insects. Science 336: 338-341.
Sasaki, T.H., H.; Ishikawa, H. (1991) Growth and reproduction of the symbiotic and aposymbiotic pea aphids, Acyrthosiphon pisum maintained on artificial diets. J Insect Physiol 37: 8.
Schmidt-Ott, U. (2005) Insect serosa: a head line in comparative developmental genetics. Curr Biol 15: R245-R247.
Schnorrer, F., Bohmann, K. and Nüsslein-Volhard, C. (2000) The molecular motor dynein is involved in targeting swallow and bicoid RNA to the anterior pole of Drosophila oocytes. Nat Cell Biol 2: 185-190.
Schoppmeier, M., Fischer, S., Schmitt-Engel, C., Lohr, U. and Klingler, M. (2009) An ancient anterior patterning system promotes caudal repression and head formation in ecdysozoa. Curr Biol 19: 1811-1815.
Schröder, R. (2003) The genes orthodenticle and hunchback substitute for bicoid in the beetle Tribolium. Nature 422: 621-625.
Schulz, C., Schröder, R., Hausdorf, B., Wolff, C. and Tautz, D. (1998) A caudal homologue in the short germ band beetle Tribolium shows similarities to both, the Drosophila and the vertebrate caudal expression patterns. Dev Genes Evol 208: 283-289.
Schulz, C. and Tautz, D. (1995) Zygotic caudal regulation by hunchback and its role in abdominal segment formation of the Drosophila embryo. Development 121: 1023-1028.
Serbus, L.R. and Sullivan, W. (2007) A cellular basis for Wolbachia recruitment to the host germline. PLoS Pathog 3: e190.
Shigenobu, S., Bickel, R.D., Brisson, J.A., Butts, T., Chang, C.-c., Christiaens, O. et al. (2010) Comprehensive survey of developmental genes in the pea aphid, Acyrthosiphon pisum: frequent lineage-specific duplications and losses of developmental genes. Insect Mol Biol 19 Suppl 2: 47-62.
Shim, J., Gururaja-Rao, S. and Banerjee, U. (2013) Nutritional regulation of stem and progenitor cells in Drosophila. Development 140: 4647-4656.
Shinmyo, Y., Mito, T., Matsushita, T., Sarashina, I., Miyawaki, K., Ohuchi, H. et al. (2005) caudal is required for gnathal and thoracic patterning and for posterior elongation in the intermediate-germband cricket Gryllus bimaculatus. Mech Dev 122: 231-239.
Small, S., Blair, A. and Levine, M. (1992) Regulation of even-skipped stripe 2 in the Drosophila embryo. EMBO J 11: 4047-4057.
Small, S., Kraut, R., Hoey, T., Warrior, R. and Levine, M. (1991) Transcriptional regulation of a pair-rule stripe in Drosophila. Genes Dev 5: 827-839.
Sonoda, J. and Wharton, R.P. (1999) Recruitment of Nanos to hunchback mRNA by Pumilio. Genes Dev 13: 2704-2712.
Spirov, A., Fahmy, K., Schneider, M., Frei, E., Noll, M. and Baumgartner, S. (2009) Formation of the bicoid morphogen gradient: an mRNA gradient dictates the protein gradient. Development 136: 605-614.
Srinivasan, D.G. and Brisson, J.A. (2012) Aphids: a model for polyphenism and epigenetics. Genet Res Int 2012: 431531.
St Johnston, D., Driever, W., Berleth, T., Richstein, S. and Nüsslein-Volhard, C. (1989) Multiple steps in the localization of bicoid RNA to the anterior pole of the Drosophila oocyte. Development 107 Suppl: 13-19.
St Johnston, D. and Nüsslein-Volhard, C. (1992) The origin of pattern and polarity in the Drosophila embryo. Cell 68: 201-219.
Starz-Gaiano, M. and Lehmann, R. (2001) Moving towards the next generation. Mech Dev 105: 5-18.
Stathopoulos, A. and Levine, M. (2002) Dorsal gradient networks in the Drosophila embryo. Dev Biol 246: 57-67.
Stauber, M., Jäckle, H. and Schmidt-Ott, U. (1999) The anterior determinant bicoid of Drosophila is a derived Hox class 3 gene. Proc Natl Acad Sci U S A 96: 3786-3789.
Stern, D.L. (2008) Aphids. Curr Biol 18: R504-R505.
Stollewerk, A., Schoppmeier, M. and Damen, W.G. (2003) Involvement of Notch and Delta genes in spider segmentation. Nature 423: 863-865.
Struffi, P., Corado, M., Kaplan, L., Yu, D., Rushlow, C. and Small, S. (2011) Combinatorial activation and concentration-dependent repression of the Drosophila even skipped stripe 3+7 enhancer. Development 138: 4291-4299.
Struhl, G., Johnston, P. and Lawrence, P.A. (1992) Control of Drosophila body pattern by the hunchback morphogen gradient. Cell 69: 237-249.
Takata, M., Sasaki, M.S., Sonoda, E., Morrison, C., Hashimoto, M., Utsumi, H. et al. (1998) Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J 17: 5497-5508.
The International Aphid Genomics Consortium (2010) Genome sequence of the pea aphid Acyrthosiphon pisum. PLoS Biol 8: e1000313.
Tomancak, P., Guichet, A., Zavorszky, P. and Ephrussi, A. (1998) Oocyte polarity depends on regulation of gurken by Vasa. Development 125: 1723-1732.
Toyooka, Y., Tsunekawa, N., Takahashi, Y., Matsui, Y., Satoh, M. and Noce, T. (2000) Expression and intracellular localization of mouse Vasa-homologue protein during germ cell development. Mech Dev 93: 139-149.
Trible, W., Olivos-Cisneros, L., McKenzie, S.K., Saragosti, J., Chang, N.C., Matthews, B.J. et al. (2017) orco mutagenesis causes loss of antennal lobe glomeruli and impaired social behavior in ants. Cell 170: 727-735.
Tsuda, M., Sasaoka, Y., Kiso, M., Abe, K., Haraguchi, S., Kobayashi, S. et al. (2003) Conserved role of nanos proteins in germ cell development. Science 301: 1239-1241.
Umulis, D.M., Serpe, M., O''Connor, M.B. and Othmer, H.G. (2006) Robust, bistable patterning of the dorsal surface of the Drosophila embryo. Proc Natl Acad Sci U S A 103: 11613-11618.
van der Zee, M., Berns, N. and Roth, S. (2005) Distinct functions of the Tribolium zerknüllt genes in serosa specification and dorsal closure. Curr Biol 15: 624-636.
van der Zee, M., Stockhammer, O., von Levetzow, C., Nunes da Fonseca, R. and Roth, S. (2006) Sog/Chordin is required for ventral-to-dorsal Dpp/BMP transport and head formation in a short germ insect. Proc Natl Acad Sci U S A 103: 16307-16312.
Via, S. (1992) Inducing the sexual forms and hatching the eggs of pea aphids. Entomol Exp Appl 65: 119-127.
Vincent, S.D., Dunn, N.R., Sciammas, R., Shapiro-Shalef, M., Davis, M.M., Calame, K. et al. (2005) The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse. Development 132: 1315-13125.
Wade, M.J. and Stevens, L. (1985) Microorganism mediated reproductive isolation in flour beetles (genus Tribolium). Science 227: 527-528.
Wagner, G.P. (2014) Homology, Genes, and Evolutionary Innovation, Course book edn. Princeton University Press, Princeton.
Wang, H., Yang, H., Shivalila, C.S., Dawlaty, M.M., Cheng, A.W., Zhang, F. et al. (2013) One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153: 910-918.
Wharton, R.P. and Struhl, G. (1991) RNA regulatory elements mediate control of Drosophila body pattern by the posterior morphogen nanos. Cell 67: 955-967.
Will, L. (1888) Entwicklungsgeschichte der viviparen Aphiden. Zool Jahrb Anat 3: 201-286.
Wilson, M.J. and Dearden, P.K. (2011) Diversity in insect axis formation: two orthodenticle genes and hunchback act in anterior patterning and influence dorsoventral organization in the honeybee (Apis mellifera). Development 138: 3497-3507.
Wilson, M.J., Havler, M. and Dearden, P.K. (2010) Giant, Krüppel, and caudal act as gap genes with extensive roles in patterning the honeybee embryo. Dev Biol 339: 200-211.
Wilson, M.J., Kenny, N.J. and Dearden, P.K. (2014) Components of the dorsal-ventral pathway also contribute to anterior-posterior patterning in honeybee embryos (Apis mellifera). EvoDevo 5: 11.
Wolff, C., Schröder, R., Schulz, C., Tautz, D. and Klingler, M. (1998) Regulation of the Tribolium homologues of caudal and hunchback in Drosophila: evidence for maternal gradient systems in a short germ embryo. Development 125: 3645-3654.
Wolff, C., Sommer, R., Schröder, R., Glaser, G. and Tautz, D. (1995) Conserved and divergent expression aspects of the Drosophila segmentation gene hunchback in the short germ band embryo of the flour beetle Tribolium. Development 121: 4227-4236.
Xu, X., Xu, P.X. and Suzuki, Y. (1994) A maternal homeobox gene, Bombyx caudal, forms both mRNA and protein concentration gradients spanning anteroposterior axis during gastrulation. Development 120: 277-285.
Yang, L., Guell, M., Byrne, S., Yang, J.L., De Los Angeles, A. et al. (2013) Optimization of scarless human stem cell genome editing. Nucleic Acids Res 41: 9049-9061.
Yen, J.H. and Barr, A.R. (1971) New hypothesis of the cause of cytoplasmic incompatibility in Culex pipiens L. Nature 232: 657-658.
Yoon, C., Kawakami, K. and Hopkins, N. (1997) Zebrafish vasa homologue RNA is localized to the cleavage planes of 2- and 4-cell-stage embryos and is expressed in the primordial germ cells. Development 124: 3157-31565.
Yu, Z., Ren, M., Wang, Z., Zhang, B., Rong, Y.S., Jiao, R. et al. (2013) Highly efficient genome modifications mediated by CRISPR/Cas9 in Drosophila. Genetics 195: 289-291.
Zundel, M.A., Basturea, G.N. and Deutscher, M.P. (2009) Initiation of ribosome degradation during starvation in Escherichia coli. RNA 15: 977-983.