Rasin Mladen-Roko, Gazula Valeswara-Rao, Breunig Joshua J, Kwan Kenneth Y, Johnson Matthew B, Liu-Chen Susan, Li Hua-Shun, Jan Lily Yeh, Jan Yuh-Nung, Rakic Pasko, Sestan Nenad
Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.
Nat Neurosci. 2007 Jul;10(7):819-27. doi: 10.1038/nn1924. Epub 2007 Jun 24.
The polarity and adhesion of radial glial cells (RGCs), which function as progenitors and migrational guides for neurons, are critical for morphogenesis of the cerebral cortex. These characteristics largely depend on cadherin-based adherens junctions, which anchor apical end-feet of adjacent RGCs to each other at the ventricular surface. Here, we show that mouse numb and numb-like are required for maintaining radial glial adherens junctions. Numb accumulates in the apical end-feet, where it localizes to adherens junction-associated vesicles and interacts with cadherins. Numb and Numbl inactivation in RGCs decreases proper basolateral insertion of cadherins and disrupts adherens junctions and polarity, leading to progenitor dispersion and disorganized cortical lamination. Conversely, overexpression of Numb prolongs RGC polarization, in a cadherin-dependent manner, beyond the normal neurogenic period. Thus, by regulating RGC adhesion and polarity, Numb and Numbl are required for the tissue architecture of neurogenic niches and the cerebral cortex.
放射状胶质细胞（RGCs）作为神经元的祖细胞和迁移向导，其极性和黏附对于大脑皮质的形态发生至关重要。这些特性很大程度上依赖于基于钙黏蛋白的黏附连接，该连接在脑室表面将相邻RGCs的顶端终足相互锚定。在此，我们表明小鼠Numb和Numb样蛋白是维持放射状胶质细胞黏附连接所必需的。Numb在顶端终足中积累，定位于与黏附连接相关的囊泡，并与钙黏蛋白相互作用。RGCs中Numb和Numbl的失活会减少钙黏蛋白正确的基底外侧插入，并破坏黏附连接和极性，导致祖细胞分散和皮质层排列紊乱。相反，Numb的过表达以依赖钙黏蛋白的方式使RGC极化延长至正常神经发生期之后。因此，通过调节RGC的黏附和极性，Numb和Numbl是神经发生微环境和大脑皮质组织结构所必需的。
