FoxJ1-dependent gene expression is required for differentiation of radial glia into ependymal cells and a subset of astrocytes in the postnatal brain
FoxJ1-dependent gene expression is required for differentiation of radial glia into ependymal cells and a subset of astrocytes in the postnatal brain
复制标题
DOI：
10.1242/dev.041129
复制
发表时间：
2009-12-01
期刊：
影响因子：
4.6
通讯作者：
Ghashghaei, H. Troy
中科院分区：
文献类型：
--
作者：
Jacquet, Benoit V.;Salinas-Mondragon, Raul;Ghashghaei, H. Troy
神经元特化发生在胚胎中枢神经系统的脑室周围表面。在出生后早期，大脑各个脑室区的放射状胶质细胞分化为室管膜细胞和星形胶质细胞。然而，驱动这种时间和细胞特异性分化的机制在很大程度上仍然未知。在这里，我们表明，叉头转录因子FoxJ1在小鼠分化为室管膜细胞和侧脑室FoxJ1（+）星形胶质细胞的一个小子集，在这些细胞形成一个出生后的神经干细胞龛所需的表达。此外，我们发现从干细胞龛中收获的FoxJ1（+）细胞亚群可以自我更新并具有神经原性潜能。使用转录组比较FoxJ1空和野生型显微组织，我们确定了候选基因FoxJ1在出生后早期发育过程中的调控。该列表包括大量的微管相关蛋白，其中一些形成蛋白质复合物，可以在FoxJ1依赖性纤毛发生期间调节基底体向分化室管膜细胞的心室表面的运输。我们的研究结果表明，FoxJ1在大脑中的时间和细胞特异性表达作用于一系列靶基因，以调节成体干细胞龛中室管膜细胞和一小部分星形胶质细胞的分化。
Neuronal specification occurs at the periventricular surface of the embryonic central nervous system. During early postnatal periods, radial glial cells in various ventricular zones of the brain differentiate into ependymal cells and astrocytes. However, mechanisms that drive this time- and cell-specific differentiation remain largely unknown. Here, we show that expression of the forkhead transcription factor FoxJ1 in mice is required for differentiation into ependymal cells and a small subset of FoxJ1(+) astrocytes in the lateral ventricles, where these cells form a postnatal neural stem cell niche. Moreover, we show that a subset of FoxJ1(+) cells harvested from the stem cell niche can self-renew and possess neurogenic potential. Using a transcriptome comparison of FoxJ1-null and wild-type microdissected tissue, we identified candidate genes regulated by FoxJ1 during early postnatal development. The list includes a significant number of microtubule-associated proteins, some of which form a protein complex that could regulate the transport of basal bodies to the ventricular surface of differentiating ependymal cells during FoxJ1-dependent ciliogenesis. Our results suggest that time- and cell-specific expression of FoxJ1 in the brain acts on an array of target genes to regulate the differentiation of ependymal cells and a small subset of astrocytes in the adult stem cell niche.