Rakotomamonjy Jennifer, Brunner Molly, Jüschke Christoph, Zang Keling, Huang Eric J, Reichardt Louis F, Chenn Anjen
Department of Pathology, University of Illinois at Chicago, 909 S Wolcott Avenue, Chicago, IL, 60612, USA.
Department of Physiology, University of California, San Francisco, 1550 4th street, San Francisco, CA, 94158-2611, USA.
Neural Dev. 2017 May 8;12(1):7. doi: 10.1186/s13064-017-0085-2.
In developing tissues, cell polarity and tissue architecture play essential roles in the regulation of proliferation and differentiation. During cerebral cortical development, adherens junctions link highly polarized radial glial cells in a neurogenic niche that controls their behavior. How adherens junctions regulate radial glial cell polarity and/or differentiation in mammalian cortical development is poorly understood.
Conditional deletion of Afadin, a protein required for formation and maintenance of epithelial tissues, leads to abnormalities in radial glial cell polarity and subsequent loss of adherens junctions. We observed increased numbers of obliquely-oriented progenitor cell divisions, increased exit from the ventricular zone neuroepithelium, and increased production of intermediate progenitors.
Together, these findings indicate that Afadin plays an essential role in regulating apical-basal polarity and adherens junction integrity of radial glial cells, and suggest that epithelial architecture plays an important role in radial glial identity by regulating mitotic orientation and preventing premature exit from the neurogenic niche.
在发育中的组织中，细胞极性和组织结构在增殖和分化的调节中起着至关重要的作用。在大脑皮质发育过程中，黏着连接将高度极化的放射状胶质细胞连接在一个控制其行为的神经发生微环境中。在哺乳动物皮质发育过程中，黏着连接如何调节放射状胶质细胞的极性和/或分化尚不清楚。
条件性敲除Afadin（一种上皮组织形成和维持所需的蛋白质）会导致放射状胶质细胞极性异常以及随后黏着连接的丧失。我们观察到倾斜定向的祖细胞分裂数量增加，从脑室区神经上皮退出的细胞增多，以及中间祖细胞的产生增加。
总之，这些发现表明Afadin在调节放射状胶质细胞的顶-基极性和黏着连接完整性方面起着至关重要的作用，并表明上皮结构通过调节有丝分裂方向和防止过早从神经发生微环境中退出，在放射状胶质细胞特性中发挥重要作用。
