Endfoot regeneration restricts radial glial state and prevents translocation into the outer subventricular zone in early mammalian brain development
Endfoot regeneration restricts radial glial state and prevents translocation into the outer subventricular zone in early mammalian brain development
复制标题
DOI：
10.1038/s41556-019-0436-9
复制
发表时间：
2019-12-23
影响因子：
21.3
通讯作者：
Matsuzaki, Fumio
中科院分区：
文献类型：
--
作者：
Fujita, Ikumi;Shitamukai, Atsunori;Matsuzaki, Fumio
神经干细胞，称为放射状胶质细胞，在早期新皮层发育过程中维持上皮结构。主流观点认为，当放射状胶质细胞首次增殖时，它们的对称分裂需要严格的纺锤体取向；它的扰动引起神经早熟和细胞凋亡。在这里，我们表明，尽管这种传统观点，放射状胶质细胞在增殖阶段通过再生根尖终足进行正常的对称分裂，即使它因斜分裂而丢失。我们发现Notch-R-Ras-integrin β 1通路促进终足的再生，其前缘具有异位粘附连接和极性复合物。然而，这种再生能力在随后的神经发生阶段逐渐下降，因此斜向分裂导致放射状胶质细胞基底移位形成外室下区，这是曲脑发育的标志。我们的研究表明，终足再生是一种暂时改变的隐性，它控制着径向神经胶质状态，其转变对哺乳动物大脑大小的扩张至关重要。Fujita等人的研究表明，放射神经胶质细胞分裂后的终足再生在早期发育中将其保留在心室区，不受纺锤体取向的影响，但在神经发生晚期丢失。
Neural stem cells, called radial glia, maintain epithelial structure during the early neocortical development. The prevailing view claims that when radial glia first proliferate, their symmetric divisions require strict spindle orientation; its perturbation causes precocious neurogenesis and apoptosis. Here, we show that despite this conventional view, radial glia at the proliferative stage undergo normal symmetric divisions by regenerating an apical endfoot even if it is lost by oblique divisions. We found that the Notch-R-Ras-integrin beta 1 pathway promotes the regeneration of endfeet, whose leading edge bears ectopic adherens junctions and the Par-polarity complex. However, this regeneration ability gradually declines during the subsequent neurogenic stage and hence oblique divisions induce basal translocation of radial glia to form the outer subventricular zone, a hallmark of the development of the convoluted brain. Our study reveals that endfoot regeneration is a temporally changing cryptic property, which controls the radial glial state and its shift is essential for mammalian brain size expansion.Fujita et al. show that endfoot regeneration of radial glia cells after division retains them in the ventricular zone in early development, independently of spindle orientation, but is lost during late neurogenesis.