Endfoot regeneration restricts radial glial state and prevents translocation into the outer subventricular zone in early mammalian brain development.,Nature Cell Biology

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Endfoot regeneration restricts radial glial state and prevents translocation into the outer subventricular zone in early mammalian brain development.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2019-12-23 , DOI: 10.1038/s41556-019-0436-9
Ikumi Fujita ₁ , Atsunori Shitamukai ₁ , Fumiya Kusumoto _{1,

2} , Shun Mase _{1,

2} , Taeko Suetsugu ₁ , Ayaka Omori ₁ , Kagayaki Kato ₃ , Takaya Abe _{4,

5} , Go Shioi ₅ , Daijiro Konno _{1,

6} , Fumio Matsuzaki _{1,

2}

Affiliation

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 β1 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.

中文翻译：

Endfoot 再生限制径向神经胶质状态并防止在哺乳动物早期大脑发育中易位到外脑室下区。

神经干细胞，称为放射状胶质细胞，在早期新皮质发育过程中维持上皮结构。普遍的观点认为，当径向胶质细胞首次增殖时，它们的对称分裂需要严格的纺锤体定向；它的扰动导致早熟的神经发生和细胞凋亡。在这里，我们表明，尽管有这种传统观点，但增殖阶段的径向胶质细胞通过再生根尖端足进行正常的对称分裂，即使它因倾斜分裂而丢失。我们发现 Notch-R-Ras-integrin β1 通路促进了尾足的再生，其前缘带有异位粘附连接和 Par 极性复合物。然而，这种再生能力在随后的神经源性阶段逐渐下降，因此斜向分裂诱导径向胶质细胞的基底易位，形成外脑室下区，这是复杂大脑发育的标志。我们的研究表明，足底再生是一种随时间变化的神秘特性，它控制着径向神经胶质状态，其转变对于哺乳动物大脑大小的扩张至关重要。

更新日期：2019-12-23

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