Foxg1 is required for specification of ventral telencephalon and region-specific regulation of dorsal telencephalic precursor proliferation and apoptosis
Foxg1 is required for specification of ventral telencephalon and region-specific regulation of dorsal telencephalic precursor proliferation and apoptosis
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DOI：
10.1016/j.ydbio.2005.04.005
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发表时间：
2005-07-01
影响因子：
2.7
通讯作者：
Mason, JO
中科院分区：
文献类型：
--
作者：
Martynoga, B;Morrison, H;Mason, JO
FOXG1基因的零突变导致小鼠端脑发育不全和腹侧端脑结构的丧失。我们表明FOXG1的一个关键早期要求是诱导端脑中腹侧细胞的命运。为了研究以后的增殖性缺陷，我们采用了碘脱氧尿苷和溴脱氧尿苷双标记方案用于发育中的胚胎，这使得在单个标本中可以估计细胞周期动力学。这项技术被用来证明在FOXG1缺失的端脑中细胞周期过早地延长。这些缺陷最早出现在胚胎第10.5天(E10.5)，最严重的部位在吻侧端脑。我们发现，在同一吻端区域，细胞凋亡也减少了。这些缺陷在时间和空间上与强大的信号分子FGF8的表达急剧减少相对应。我们还表明，在没有FOXG1的情况下，E11.5产生了过量的神经元，耗尽了祖细胞池并限制了FOXG1(-/-)端脑的生长。神经源性分裂的增加与BMP信号的增加是一致的，正如磷酸化的Smad-1、-5和-8的免疫组织化学检测到的那样。本研究进一步证实了FOXG1作为端脑神经发生的主要调控因子的地位，并支持FOXG1通过调控成纤维细胞生长因子信号调控前体细胞增殖，通过调控BMP信号调控神经前体细胞分化的观点。(C)2005 Elsevier Inc.保留所有权利。
Null mutation of the Foxg1 gene causes hypoplasia of the mouse telencephalon and loss of ventral telencephalic structures. We show that a crucial early requirement for Foxg1 is in the induction of ventral cell fate in the telencephalon. To study later proliferative defects, we have adapted an iododeoxyuridine and bromodeoxyuridine double labeling protocol for use in the developing embryo, which allows estimation of cell cycle kinetics in a single specimen. This technique is used to demonstrate that the cell cycle is prematurely lengthened in the Foxg1-null telencephalon. These defects are first apparent at embryonic day 10.5 (E10.5) and are most severe in the rostral telencephalon. We show that apoptosis is also reduced in the same rostral domain. These defects correspond temporally and spatially with a dramatic reduction in expression of the potent signaling molecule Fgf 8. We also show that in the absence of Foxg1 an excess of neurons is produced from E 11.5, depleting the progenitor pool and limiting the growth of the Foxg1(-/-) telencephalon. The increase in neurogenic division coincides with an increase in BMP signaling, as detected by immunohistochemistry for phosphorylated smad-1, -5, and -8. This study reinforces Foxg1's position as a major regulator of telencephalie neurogenesis and supports the idea that Foxg1 controls precursor proliferation via regulation of Fgf signaling and differentiation via regulation of Bmp signaling. (C) 2005 Elsevier Inc. All rights reserved.