Dentate gyrus development requires a cortical hem-derived astrocytic scaffold.
Dentate gyrus development requires a cortical hem-derived astrocytic scaffold.
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DOI：
10.7554/elife.63904
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发表时间：
2021-01-04
期刊：
影响因子：
7.7
通讯作者：
Lovell-Badge R
中科院分区：
文献类型：
--
作者：
Caramello A;Galichet C;Rizzoti K;Lovell-Badge R
在胚胎发育过程中，放射状胶质细胞产生神经元，然后在胶质发生转换后产生星形胶质细胞。由几个转录因子操作的开关的及时调节是允许神经元和胶质细胞之间协调相互作用的基础。我们删除了这样一个因子，SOX 9，在小鼠大脑发育的早期，并观察到一个显着受损的齿状回（DG）的基因。我们解剖了缺陷的起源，将胚胎Sox9缺失定位于DG神经元祖细胞结构域或相邻的皮质边缘（CH）。我们确定在后者以前未表征的ALDH1L1+星形胶质细胞祖细胞，形成一个菌毛特异性神经胶质细胞支架神经元祖细胞向发展DG迁移所必需的。我们的研究结果突出了早期的关键作用，SOX 9 DG的发展，通过调节星形胶质细胞的潜力收购CH。此外，我们说明了如何形成一个本地网络，星形胶质细胞和神经元祖细胞起源于相邻的域，大脑形态发生的基础。
During embryonic development, radial glial cells give rise to neurons, then to astrocytes following the gliogenic switch. Timely regulation of the switch, operated by several transcription factors, is fundamental for allowing coordinated interactions between neurons and glia. We deleted the gene for one such factor, SOX9, early during mouse brain development and observed a significantly compromised dentate gyrus (DG). We dissected the origin of the defect, targeting embryonic Sox9 deletion to either the DG neuronal progenitor domain or the adjacent cortical hem (CH). We identified in the latter previously uncharacterized ALDH1L1+ astrocytic progenitors, which form a fimbrial-specific glial scaffold necessary for neuronal progenitor migration toward the developing DG. Our results highlight an early crucial role of SOX9 for DG development through regulation of astroglial potential acquisition in the CH. Moreover, we illustrate how formation of a local network, amidst astrocytic and neuronal progenitors originating from adjacent domains, underlays brain morphogenesis.