Cortical neural precursors inhibit their own differentiation via N-cadherin maintenance of beta-catenin signaling

皮质神经前体通过 N-钙粘蛋白维持 β-连环蛋白信号传导来抑制自身分化

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作者:Jianing Zhang, Gregory J Woodhead, Sruthi K Swaminathan, Stephanie R Noles, Erin R McQuinn, Anna J Pisarek, Adam M Stocker, Christopher A Mutch, Nobuo Funatsu, Anjen Chenn

Abstract

Little is known about the architecture of cellular microenvironments that support stem and precursor cells during tissue development. Although adult stem cell niches are organized by specialized supporting cells, in the developing cerebral cortex, neural stem/precursor cells reside in a neurogenic niche lacking distinct supporting cells. Here, we find that neural precursors themselves comprise the niche and regulate their own development. Precursor-precursor contact regulates beta-catenin signaling and cell fate. In vivo knockdown of N-cadherin reduces beta-catenin signaling, migration from the niche, and neuronal differentiation in vivo. N-cadherin engagement activates beta-catenin signaling via Akt, suggesting a mechanism through which cells in tissues can regulate their development. These results suggest that neural precursor cell interactions can generate a self-supportive niche to regulate their own number.

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