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研究生:陳克儉
研究生(外文):Ko-Chien Chen
論文名稱:結締組織生長因子在小鼠大腦皮質中所扮演的角色
論文名稱(外文):The Roles of Connective Tissue Growth Factor in the Cerebral Cortex of Mice
指導教授:李立仁李立仁引用關係
指導教授(外文):Li-Jen Lee
口試委員:王培育呂俊宏
口試委員(外文):Pei-Yu WangJune-Horng Lue
口試日期:2015-07-09
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:解剖學暨細胞生物學研究所
學門:醫藥衛生學門
學類:醫學學類
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:53
中文關鍵詞:結締組織生長因子底板寡突細胞
外文關鍵詞:Connective tissue growth factorsubplateoligodendrocytes
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結締組織生長因子(CTGF)是一種分泌性的胞外基質相關蛋白,在細胞功能調控上扮演許多角色。雖然如此,但是現今對於CTGF的功能研究主要還是在非神經組織上,而中樞神經系統中的CTGF所扮演的角色仍然不清楚。目前只知道,在中樞神經系統中,CTGF會表現於皮質底板上(cortical subplate)。因此,為了研究大腦中CTGF的功能,我們使帶有Ctgfflox/flox的基因轉殖小鼠與帶有Emx1-Cre的基因轉殖小鼠交配,所產出的後代小鼠的前腦(forebrain, Fb),在出生前即表現重組脢蛋白(Cre)以達到Ctgf基因剔除(knockout, KO)的目的,利用此Ctgf前腦專一性剔除(FbCtgf KO)小鼠來做為本次實驗的研究對象。 我們利用免疫組織化學染色法來觀察幼鼠(4-5 weeks)與成鼠(10-12 weeks 以及16-18 weeks)體感皮質區(somatosensory cortex)中的神經細胞分布,藉此分析CTGF在維持皮質層以及皮質層發育上的功能為何。實驗結果顯示,在細胞分佈方面,包括神經細胞(neurons)與神經膠細胞(neural glia),FbCtgf KO小鼠與野生型小鼠並沒有差異。近來不論是in vitro或是in vivo的研究皆顯示,CTGF的存在會抑制寡突細胞(oligodendrocytes)的分化。我們發現,比起野生型小鼠,在FbCtgf KO成鼠的大腦白質外囊(external capsule)中,有較多的成熟寡突細胞,此結果顯示了CTGF會抑制寡突細胞的成熟過程。

Connective tissue growth factor (CTGF) is a secreted extracellular matrix-associated protein that plays various roles in the regulation of cellular functions. While the roles of CTGF have been well-characterized in non-neural tissues, little is known regarding its function in the CNS. It has been reported that CTGF is expressed in the cortical subplate, but its role is still unknown. Thus, to explore the function of CTGF in the brain, a forebrain-specific Ctgf knockout (FbCtgf KO) mouse model was generated by crossing Ctgfflox/flox mice with Emx1-Cre transgenic mice in which the expression of Cre is prenatally initiated and the full length Ctgf is removed in the forebrain structures. We performed immunohistochemistry analyses to characterize neural patterning of the somatosensory cortex of juvenile (4-5 weeks) and adult (10-12 weeks and 16-18 weeks) mice to determine the effect of CTGF on the development and/or maintenance of cortical layers. Our results showed that the distribution of neurons and glia in FbCtgf KO mice did not exhibit differences compared to wild-type mice. Recent in vitro and in vivo studies have shown that CTGF hinders the differentiation of oligodendrocytes. In our mouse model, greater number of mature oligodendrocytes in the external capsule was noticed in adult FbCtgf KO mice, compared to wild-type mice, suggesting an inhibitory role of CTGF in the maturation of oligodendrocytes.

致謝 i
中文摘要 ii
Abstract iii
Contents iv
Chapter 1 Introduction 1
1.1 Connective tissue growth factor 1
1.2 Subplate and its role in cortical development 4
1.3 Connective tissue growth factor and oligodendrocytes 6
Chapter 2 Materials and Methods 7
2.1 Animals 7
2.2 Generation and genotyping of FbCtgf KO mice 7
2.3 Preparation of tissue sections 9
2.4 Measurement of neural cells of the somatosensory cortex 10
2.5 Transmission electron microscopy 12
2.6 Statistical analysis 12
Chapter 3 Results 13
3.1 Generation of forebrain-specific Ctgf Knockout Mice 13
3.2 Expression of subplate markers 14
3.3 Cortical neuronal patterning in juvenile mice 14
3.4 Cortical neuronal patterning in adult mice 16
3.5 Expression of glial markers in the cortex of adult mice 17
3.6 Oligodendrocyte markers in the cortex of adult mice 18
3.7 CTGF regulates differentiation of oligodendrocytes 19
Chapter 4 Discussion 21
4.1 Subplate-derived Ctgf is independent of neural patterning during cortical development 21
4.2 Subplate-derived Ctgf in adult brain 21
4.3 CTGF regulates the differentiation of oligodendrocyte progenitor cells 23
4.4 Secretory function of subplate neurons 25
Reference 26
Figures 32

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