Fstl1参与放射胶质细胞“支架”的发育调控

发布时间：2018-06-01 17:21

本文选题：Fstl1 + 大脑皮质分层　；参考：《东南大学》2016年博士论文

【摘要】：放射胶质细胞(Radial glial cells, RGCs)在大脑皮质的发育过程中为神经元放射状迁移提供“支架”。这类细胞具有独特形态和典型的双极性特征,其胞体basal面伸出一根长突起并指向软脑膜方向彼此平行排列。然而对放射胶质细胞这种独特的形态特征的发育调控和维持机制我们所知甚少。我们通过将Fstl1fl/fl小鼠与Ella-Cre小鼠交配获得Fstl1-/-基因敲除小鼠,使来源于脑室区(ventricular zone, VZ)和软脑膜的分泌性糖蛋白卵泡抑素样蛋白-1(Follistatin like-1, FSTL1)均缺失功能,从而首次揭示了Fstl1在大脑皮质发育过程中的功能。首先,Fstl1缺失导放射胶质支架排列紊乱,同时其顶端“终足”结构提前分支且分支结构复杂性增加。其次,对Emx 1IRScre; Fstl 1fl/fl条件性基因敲除小鼠的研究表明,仅缺失VZ区来源的FSTL1而保留软脑膜来源的FSTL1,放射胶质细胞形态发育不受影响。并且,缺失FSTL1会导致大脑皮质浅层兴奋性神经元放射状迁移过程受到阻滞,但不影响深层兴奋性神经元迁移。分子机制研究表明,缺失FSTL1不影响一些公认的RGCs发育的调控信号,如BNP、AKT/PKB、 Cdc42、GSK3β、integrin and reelin蛋白等,提示我们Fstl1可能是通过特殊的未知信号通路调控RGCs发育。在本课题的研究中,我们团队首次揭示了FSTL1在大脑皮质放射胶质支架发育和皮质浅层兴奋性投射神经元放射状迁移中的功能,为更好地理解放射胶质细胞发育、神经元放射状迁移和大脑皮质板层分层结构形成的调控机制提供新的思路和有益的参考。
[Abstract]:Radial glial cells, RGCs) provides a "scaffold" for the radial migration of neurons during the development of cerebral cortex. These cells have unique morphology and typical bipolar characteristics. The basal plane of the cell body protrudes a long protuberance and is parallel to each other in the direction of the pia meninges. However, little is known about the developmental, regulatory and maintenance mechanisms of this unique morphological feature of radioblastoma. We mated Fstl1fl/fl mice with Ella-Cre mice to obtain Fstl1-r-gene knockout mice, which deleted the function of secretory glycoprotein follistatin like-1 (FSTL1), which originated from the ventricular area of ventricular area, VZ1, and pial meninges. Thus, the function of Fstl1 in the development of cerebral cortex is revealed for the first time. At first, the Fstl1 missing conductance scaffold was disordered, and the terminal foot structure branched earlier and the branching structure complexity increased. Secondly, the study of Emx 1 IRScre; Fstl 1fl/fl conditional gene knockout mice showed that the morphological development of radionuclide cells was not affected by the deletion of FSTL1 from VZ region but the preservation of pterymoma origin FSTL 1. Moreover, the absence of FSTL1 could block the radial migration of the superficial excitatory neurons in the cerebral cortex, but it did not affect the migration of the deep excitatory neurons. Molecular mechanism studies indicate that the absence of FSTL1 does not affect some recognized regulatory signals of RGCs development, such as BNPAKT / PKB, Cdc42GST-GSK3 尾 integrin and reelin protein, suggesting that our Fstl1 may regulate RGCs development through a special unknown signaling pathway. In this study, our team for the first time revealed the role of FSTL1 in the development of glial stents in the cerebral cortex and the radial migration of excitatory projective neurons in the superficial cortex, in order to better understand the development of radionuclide cells. The regulation mechanism of neuronal radial migration and lamellar stratification of cerebral cortex provides new ideas and useful references.
【学位授予单位】：东南大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：Q23

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