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LGL1 binds to Integrin β1 and inhibits downstream signaling to promote epithelial branching in the mammary gland

Cell Rep. 2022-02; 
Rongze Ma , Difei Gong , Huanyang You , Chongshen Xu , Yunzhe Lu , Gabriele Bergers , Zena Werb , Ophir D Klein , Claudia K Petritsch , Pengfei Lu
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摘要

Branching morphogenesis is a fundamental process by which organs in invertebrates and vertebrates form branches to expand their surface areas. The current dogma holds that directional cell migration determines where a new branch forms and thus patterns branching. Here, we asked whether mouse Lgl1, a homolog of the Drosophila tumor suppressor Lgl, regulates epithelial polarity in the mammary gland. Surprisingly, mammary glands lacking Lgl1 have normal epithelial polarity, but they form fewer branches. Moreover, we find that Lgl1 null epithelium is unable to directionally migrate, suggesting that migration is not essential for mammary epithelial branching as expected. We show that LGL1 binds to Integrin β1 and i... More

关键词

branching morphogenesis; collective migration; epithelial migration; epithelial polarity; extracellular matrix; integrin signaling; tumor-suppressor genes.