A mutually stimulating loop involving Emx2 and canonical wnt signalling specifically promotes expansion of occipital cortex and hippocampus
A mutually stimulating loop involving Emx2 and canonical wnt signalling specifically promotes expansion of occipital cortex and hippocampus
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DOI：
10.1093/cercor/bhi077
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发表时间：
2005-12-01
期刊：
影响因子：
3.7
通讯作者：
Mallamaci, A
中科院分区：
文献类型：
--
作者：
Muzio, L;Soria, JM;Mallamaci, A
组成成熟大脑皮层的不同区域的正确大小取决于皮质祖细胞对其独特的区域命运的适当早期分配，以及随后对其特定区域的增殖分化特征的适当调整。虽然对前一过程的遗传学已知很多，但调节独特的皮质原生区内的增殖和分化率的分子机制仍然很不清楚。在这里，我们显示了一个相互刺激的环路，涉及Emx2和规范的Wnt信号，特别促进枕海马神经原的扩张。Emx2(-/-)突变体中这一环的崩溃导致该区域内的祖细胞减慢DNA合成，并由于细胞周期、神经和侧向抑制分子机制的错误调节而过早退出细胞周期，最终导致枕叶皮质和海马区显著和选择性的尺寸缩小。在相同的突变体中重新激活规范的Wnt信号可以挽救分子异常的一个子集，并纠正枕海马祖细胞的分化率。
The correct size of the different areas composing the mature cerebral cortex depends on the proper early allocation of cortical progenitors to their distinctive areal fates, as well as on appropriate subsequent tuning of their area-specific proliferation-differentiation profiles. Whereas much is known about the genetics of the former process, the molecular mechanisms regulating proliferation and differentiation rates within distinctive cortical proto-areas are still largely obscure. Here we show that a mutual stimulating loop, involving Emx2 and canonical Wnt signalling, specifically promotes expansion of the occipito-hippocampal anlage. Collapse of this loop occurring in Emx2(-/-) mutants leads progenitors within this region to slow down DNA synthesis and exit prematurely from the cell cycle, due to misregulation of cell cycle-, proneural- and lateral inhibition-molecular machineries, and eventually results in dramatic and selective size-reduction of occipital cortex and hippocampus. Reactivation of canonical Wnt signalling in the same mutants rescues a subset of molecular abnormalities and corrects differentiation rates of occipito-hippocampal progenitors.