Rac1 deficiency in the forebrain results in neural progenitor reduction and microcephaly.
Rac1 deficiency in the forebrain results in neural progenitor reduction and microcephaly.
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DOI：
10.1016/j.ydbio.2008.10.023
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发表时间：
2009-01-01
影响因子：
2.7
通讯作者：
Zheng, Yi
中科院分区：
文献类型：
--
作者：
Chen, Lei;Melendez, Jaime;Campbell, Kenneth;Kuan, Chia-Yi;Zheng, Yi
小gtpase的Rho家族与许多神经系统疾病有关，包括智力迟钝，但它们是否与原发性小头畸形（真性小头症）有关尚不清楚。在这里，我们研究了Rac1在哺乳动物神经祖细胞和前脑发育中的作用，通过条件基因靶向策略，使用Foxg1-Cre系删除小鼠胚胎中远端脑室区（VZ）的弯曲Rac1等位基因。我们发现，端脑VZ祖细胞中的Rac1缺失导致纹状体和大脑皮层的大小减小。进一步分析表明，这种异常是由早期皮质形成过程中细胞周期退出加速和细胞凋亡增加引起的（约E14.5），导致端脑发育中后期神经祖细胞池减少（E16.5至E18.5）。此外，由于缺乏rac1，纹状体中斑块基质室室的形成受到损害。综上所述，这些结果表明Rac1调节端脑神经祖细胞的自我更新、存活和分化，Rac1功能障碍可能导致原发性小头畸形。
The Rho family of small GTPases has been implicated in many neurological disorders including mental retardation, but whether they are involved in primary microcephaly (microcephalia vera) is unknown. Here, we examine the role of Rac1 in mammalian neural progenitors and forebrain development by a conditional gene-targeting strategy using the Foxg1-Cre line to delete floxed-Rac1 alleles in the telencephalic ventricular zone (VZ) of mouse embryos. We found that Rac1 deletion in the telencephalic VZ progenitors resulted in reduced sizes of both the striatum and cerebral cortex. Analyses further indicated that this abnormality was caused by accelerated cell-cycle exit and increased apoptosis during early corticogenesis (approximately E14.5), leading to a decrease of the neural progenitor pool in mid-to-late telencephalic development (E16.5 to E18.5). Moreover, the formation of patch-matrix compartments in the striatum was impaired by Rac1-deficiency. Together, these results suggest that Rac1 regulates self-renewal, survival, and differentiation of telencephalic neural progenitors, and that dysfunctions of Rac1 may lead to primary microcephaly.
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影响因子：
56.9
作者：
Gu, Y;Filippi, MD;Williams, DA
通讯作者：
Williams, DA
DOI：
10.1073/pnas.82.24.8780
发表时间：
1985-12-01
影响因子：
11.1
作者：
GERFEN, CR;BAIMBRIDGE, KG;MILLER, JJ
通讯作者：
MILLER, JJ
DOI：
10.1073/pnas.0603533103
发表时间：
2006-10-31
影响因子：
11.1
作者：
Chen, Lei;Liao, Guanghong;Zheng, Yi
通讯作者：
Zheng, Yi
影响因子：
9.8
作者：
Bond, J;Scott, S;Woods, CG
通讯作者：
Woods, CG
影响因子：
9.8
作者：
Jackson, AP;Eastwood, H;Woods, CG
通讯作者：
Woods, CG