Profilin1-Dependent F-Actin Assembly Controls Division of Apical Radial Glia and Neocortex Development
Profilin1-Dependent F-Actin Assembly Controls Division of Apical Radial Glia and Neocortex Development
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DOI：
10.1093/cercor/bhz321
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发表时间：
2020-06-01
期刊：
影响因子：
3.7
通讯作者：
Rust, Marco B.
中科院分区：
文献类型：
--
作者：
Kullmann, Jan A.;Meyer, Sophie;Rust, Marco B.
新皮层的发育依赖于神经干细胞的增殖、分化、神经发生和神经元迁移。细胞骨架调节对于所有这些过程都是至关重要的，但其潜在的机制却知之甚少。我们以前牵连的细胞骨架调节profilin1在小脑颗粒神经元迁移。由于我们发现profilin1在整个小鼠新皮层发育过程中表达，我们在这里测试了profilin1对新皮层发育至关重要的假设。我们没有发现profilin1突变小鼠新皮层神经元迁移或分层受损的证据。然而，在神经发生中期，突变的新皮层基底部位的增殖活性加倍，基底Pax6（+）细胞的急剧和特异性增加表明基底放射状胶质细胞（bRG）数量增加。这伴随着短暂的神经发生增加，并与轻度内陷类似于基本的新皮质褶皱。我们的数据是在一个模型中，profilin1依赖的肌动蛋白组件控制顶端放射状胶质细胞（aRG）的分裂，从而其后代的命运。通过这种机制，profilin1限制细胞Co从心室表面分层，因此，bRG生产，从而控制小鼠新皮质发育。我们的数据支持径向锥假说，声称升高bRG数量导致新皮质褶皱。
Neocortex development depends on neural stem cell proliferation, cell differentiation, neurogenesis, and neuronal migration. Cytoskeletal regulation is critical for all these processes, but the underlying mechanisms are only poorly understood. We previously implicated the cytoskeletal regulator profilin1 in cerebellar granule neuron migration. Since we found profilin1 expressed throughout mouse neocortex development, we here tested the hypothesis that profilin1 is crucial for neocortex development. We found no evidence for impaired neuron migration or layering in the neocortex of profilin1 mutant mice. However, proliferative activity at basal positions was doubled in the mutant neocortex during mid-neurogenesis, with a drastic and specific increase in basal Pax6(+) cells indicative for elevated numbers of basal radial glia (bRG). This was accompanied by transiently increased neurogenesis and associated with mild invaginations resembling rudimentary neocortex folds. Our data are in line with a model in which profilin1-dependent actin assembly controls division of apical radial glia (aRG) and thereby the fate of their progenies. Via this mechanism, profilin1 restricts cell Co delamination from the ventricular surface and, hence, bRG production and thereby controls neocortex development in mice. Our data support the radial cone hypothesis claiming that elevated bRG number causes neocortex folds.