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研究生:王惠民
研究生(外文):Hui-Min Wang
論文名稱:探討新型自主感光視神神經細胞之發育及其功能
論文名稱(外文):Determine the Developmental Lineage and Functions of Novel Retinal Photoreceptors
指導教授:陳示國
指導教授(外文):Shih-Kuo Chen
口試委員:王致恬林頌然周申如
口試日期:2015-07-02
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:生命科學系
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:英文
論文頁數:63
中文關鍵詞:Brn3b 陰性 M1 型自主感光視神神經細胞視交叉上核視網 膜發育生理理時鐘
外文關鍵詞:brn3b negative M1 intrinsically photosensitive retinal ganglion cellssuprachiasmatic nucleusretinal developmentcell birthdatecircadian rhythm
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自從視黑質被發現後,自主感光視神神經細胞(ipRGCs)被發現參參與了了 許多非成像視覺功能,例例如生理理週期及瞳孔光反射。在視神神經細胞的 發育中,brn3b (POU4F2) 是個常見見的轉錄錄因子。儘管大部份的 ipRGCs 表現 brn3b,卻有少部分的 ipRGCs 不不表現 brn3b,這些 ipRGCs 主 要支配了了下視丘中的視交叉上核(SCN),而 SCN 的功能為哺乳類類動 物的生理理時鐘中樞。在視網膜發育的過程中,不不同時間點分化出來來的 細胞往往形成不不同的細胞種類類。為了了找出這些 brn3b 陰性 ipRGCs 的 分化時程,我們利利用缺乏 brn3b 陽性 ipRGCs 的基因轉殖小鼠,以及 野生型小鼠,以 5-乙炔基-2’-去氧尿尿苷(EdU)和視黑質免疫染色來來標 定在特定時間點進行行細胞分裂裂的 ipRGCs。我們的資料料顯示 brn3b 陰 性 ipRGCs 與全體的 ipRGCs,從前驅細胞分化出來來的時間範圍並無 顯著差異異。更更進一步分析這些細胞的分佈範圍,發現 brn3b 陰性 ipRGCs 與全體 ipRGCs 在發育的空間進程上有些微的差異異。另一方 面,針對 brn3b 陰性 ipRGCs 與視交叉上核所主導的生理理時鐘,藉由 雙眼及單眼的生理理時鐘相位移實驗的結果,提供日後相關研究的參參 考。


Since the melanopsin was discovered, the novel photoreceptor, melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), have been shown to participate in many non-image forming functions such as circadian rhythms and pupillary light reflex. While most ipRGCs express brn3b (POU4F2), the general transcription factor for retinal ganglion cells development, a portion of ipRGCs do not express brn3b and dominantly innervate suprachiasmatic nucleus (SCN), which is the central clock for circadian rhythm in mammals. In retinal development, different time points of cell differentiation strongly imply different cell types. To identify differentiation time point of brn3b negative ipRGCs, we used 5-ethynyl-2’-deoxyuridine (EdU) and melanopsin immunostaining to label mitotic ipRGCs at specific embryonic stage in wild type mice and transgenic mice without brn3b-expressing ipRGCs. Our data show that brn3b negative ipRGCs and the whole population of ipRGCs derive from retinal progenitor cells in the same period. Further analysis in spatial
iii
distribution discovered slight difference at progression of development. In addition, to assess the circadian rhythms that brn3b negative M1 ipRGCs and SCN involve, circadian phase shift experiments of one-eye light pulse and two-eye light pulse were done, and the results provide some insights for researches in the future.

謝誌 ...................................................................................................................................... I
摘要 ..................................................................................................................................... II
ABSTRACT........................................................................................................................ III
CONTENTS ........................................................................................................................ V
CHAPTER I INTRODUCTION ......................................................................................... 1 CIRCADIAN RHYTHM................................................................................................................ 1 RETINA STRUCTURE AND DEVELOPMENT ................................................................................ 4 INTRINSICALLY PHOTOSENSITIVE RETINAL GANGLION CELLS- IPRGCS ................................ 8 SUPRACHIASMATIC NUCLEUS AND CIRCADIAN RHYTHMS.................................................... 11
STATEMENT OF PURPOSE ............................................................................................13 CHAPTER II MATERIALS AND METHODS .................................................................15
ANIMALS ................................................................................................................................ 15 EDU INJECTION ...................................................................................................................... 17 RETINA DISSECTION AND STAINING ...................................................................................... 18
v
Z/EG MOUSE LINE AND FLUORESCENT IPRGCS ..................................................................... 21 RETINA SPECIMEN IMAGING AND CELL CALCULATION .......................................................... 22 BEHAVIORAL EXPERIMENT .................................................................................................... 23
CHAPTER III RESULTS ..................................................................................................25 NUMBERS OF STAINED CELLS ................................................................................................. 25 BIRTHDATES OF BRN3B NEGATIVE M1 IPRGCS ..................................................................... 26 SPATIAL DISTRIBUTION OF BRN3B NEGATIVE M1 IPRGCS AND ALL IPRGCS ....................... 29 SPATIAL DISTRIBUTION OF BRN3B NEGATIVE M1 IPRGCS AND ALL IPRGCS LABELLED BY EDU INJECTED ON EACH DAY ................................................................................................. 30 PHASE SHIFTS OF 125 LUX OR 250 LUX LIGHT PULSES ON ONE EYE OR TWO EYES ................. 32 NUMBERS OF IPRGCS IN NEONATAL MOUSE RETINAE ......................................................... 33
CHAPTER IV DISCUSSION.............................................................................................34 REFERENCES ...................................................................................................................60

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