Jacquet Benoit V, Salinas-Mondragon Raul, Liang Huixuan, Therit Blair, Buie Justin D, Dykstra Michael, Campbell Kenneth, Ostrowski Lawrence E, Brody Steven L, Ghashghaei H Troy
North Carolina State University, College of Veterinary Medicine, Department of Molecular Biomedical Sciences, Raleigh, NC 27606, USA.
Development. 2009 Dec;136(23):4021-31. doi: 10.1242/dev.041129.
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.
神经元特化发生在胚胎中枢神经系统的室管膜表面。在出生后的早期阶段，大脑各个脑室区域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，小鼠中叉头转录因子FoxJ1的表达对于侧脑室室管膜细胞和一小部分FoxJ1(+)星形胶质细胞的分化是必需的，这些细胞在出生后形成神经干细胞微环境。此外，我们表明，从干细胞微环境中收获的一部分FoxJ1(+)细胞可以自我更新并具有神经发生潜力。通过对FoxJ1基因敲除和野生型显微切割组织进行转录组比较，我们确定了出生后早期发育过程中受FoxJ1调控的候选基因。该列表包括大量微管相关蛋白，其中一些形成蛋白复合物，在依赖FoxJ1的纤毛发生过程中，该复合物可能调节基体向分化的室管膜细胞脑室表面的运输。我们的结果表明，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，以调节成体干细胞微环境中室管膜细胞和一小部分星形胶质细胞的分化。
