Phosphatidylinositol transfer protein/planar cell polarity axis regulates neocortical morphogenesis by supporting interkinetic nuclear migration.
Phosphatidylinositol transfer protein/planar cell polarity axis regulates neocortical morphogenesis by supporting interkinetic nuclear migration.
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DOI：
10.1016/j.celrep.2022.110869
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发表时间：
2022-05-31
期刊：
影响因子：
8.8
通讯作者：
Bankaitis, Vytas A.
中科院分区：
文献类型：
--
作者：
Xie, Zhigang;Bankaitis, Vytas A.
新皮层在胚胎发育期间爆炸性地膨胀。最早的神经干细胞（NSCs）群体形成一个薄的假复层上皮，其轮廓决定了成年新皮层的轮廓。新皮质的复杂性伴随着NSC层在其切线方向上的不成比例的扩张，以增加组织表面积。如何控制这种不成比例的扩张仍然是未知的。我们证明，磷脂酰肌醇转移蛋白（PITP）/非经典Wnt平面细胞极性（ncPCP）信号轴促进切向扩张的发展中的新皮层。PITP信号支持特定ncPCP受体从NSC高尔基体系统的运输，以增强肌动球蛋白活性，这对细胞周期依赖性核间迁移（IKNM）很重要。反过来，IKNM促进新生NSC的侧向分散和脑壁的切线生长。这些研究结果阐明了IKNM在NSC生物学中的功能作用，并确定了IKNM受损导致的组织畸形，作为自闭症风险，发育性脑残疾和神经管出生缺陷的一个因素。Xie和Bankaitis报道磷脂酰肌醇转移蛋白/非典型平面细胞极性信号传导轴通过促进特定非典型平面细胞极性受体从高尔基体系统向质膜的运输、激活肌动球蛋白和通过会聚延伸机制支持新皮质的侧向扩张来支持动力学间核迁移。
The neocortex expands explosively during embryonic development. The earliest populations of neural stem cells (NSCs) form a thin pseudostratified epithelium whose contour determines that of the adult neocortex. Neocortical complexity is accompanied by disproportional expansion of the NSC layer in its tangential dimension to increase tissue surface area. How such disproportional expansion is controlled remains unknown. We demonstrate that a phosphatidylinositol transfer protein (PITP)/non-canonical Wnt planar cell polarity (ncPCP) signaling axis promotes tangential expansion of developing neocortex. PITP signaling supports trafficking of specific ncPCP receptors from the NSC Golgi system to potentiate actomyosin activity important for cell-cycle-dependent interkinetic nuclear migration (IKNM). In turn, IKNM promotes lateral dispersion of newborn NSCs and tangential growth of the cerebral wall. These findings clarify functional roles for IKNM in NSC biology and identify tissue dysmorphogenesis resulting from impaired IKNM as a factor in autism risk, developmental brain disabilities, and neural tube birth defects. Xie and Bankaitis report that a phosphatidylinositol transfer protein/non-canonical planar cell polarity signaling axis supports interkinetic nuclear migration by promoting trafficking of specific non-canonical planar cell polarity receptors from the Golgi system to the plasma membrane, activating actomyosin, and supporting lateral expansion of the neocortex via a convergent extension mechanism.
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