Department of Biomedical Science; Florida State University College of Medicine; Tallahassee, Florida USA.
Organogenesis. 2007 Oct;3(2):93-101. doi: 10.4161/org.3.2.5171.
Radial glia cells are the first distinguishable glial population derived from neural epithelial cells and serve as guides for migrating neurons and as neural progenitor cells in the developing brain. Despite their functional importance during neural development, the determination and differentiation of these cells remains poorly understood at the molecular level. Ets-1 and Ets-2, Ets (E26 transformation-specific) transcription factors, are vertebrate homologues of Drosophila pointed, which is expressed in a subset of glia cells and promotes different aspects of Drosophila glia cell differentiation. However, it remains unsolved that the function of Ets genes is conserved in vertebrate glia development. Here we report that Ets-1 but not Ets-2 is necessary for Xenopus radial glia formation and the activity of Ets-1 is sufficient for radial glia formation prior to neural tube closure. Furthermore, we show that Ras-MAPK (mitogen activated protein kinase) signaling, which acts as an upstream activator of Ets-1 in other biological processes, also regulates radial glia formation. A mutant form of Ets-1, which is not responsive to Ras-MAPK signaling, inhibits radial glia formation promoted by Ras-MAPK signaling. Together, our results show that Ets-1 activated by Ras-MAPK signaling promotes radial glia formation during Xenopus embryogenesis.
放射状胶质细胞是最早从神经上皮细胞分化而来的胶质细胞群体,它们作为迁移神经元的引导,同时也是发育中大脑中的神经祖细胞。尽管它们在神经发育过程中具有重要的功能,但这些细胞的决定和分化在分子水平上仍未被很好地理解。Ets-1 和 Ets-2 是 Ets(E26 转化特异性)转录因子的脊椎动物同源物,是果蝇 pointed 的同源物,在一部分神经胶质细胞中表达,并促进果蝇神经胶质细胞分化的不同方面。然而,Ets 基因在脊椎动物神经胶质发育中的功能是否保守仍未解决。在这里,我们报告 Ets-1 但不是 Ets-2 对于 Xenopus 放射状胶质细胞的形成是必需的,并且 Ets-1 的活性足以在神经管闭合之前形成放射状胶质细胞。此外,我们还表明,Ras-MAPK(丝裂原激活的蛋白激酶)信号通路,它在其他生物过程中作为 Ets-1 的上游激活剂,也调节放射状胶质细胞的形成。一种对 Ras-MAPK 信号不敏感的 Ets-1 突变形式,抑制了由 Ras-MAPK 信号促进的放射状胶质细胞形成。总之,我们的结果表明,Ras-MAPK 信号激活的 Ets-1 促进了 Xenopus 胚胎发生过程中的放射状胶质细胞形成。