RESUMO
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 ß1 and inhibits its downstream signaling, and Integrin ß1 overexpression blocks epithelial migration, thus recapitulating the Lgl1 null phenotype. Altogether, we demonstrate that Lgl1 modulation of Integrin ß1 signaling is essential for directional migration and that epithelial branching in invertebrates and the mammary gland is fundamentally distinct.
Assuntos
Epitélio , Glicoproteínas , Integrina beta1 , Glândulas Mamárias Animais , Morfogênese , Transdução de Sinais , Animais , Movimento Celular/genética , Polaridade Celular , Proliferação de Células , Regulação para Baixo , Células Epiteliais/metabolismo , Epitélio/crescimento & desenvolvimento , Feminino , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/metabolismo , Integrina beta1/metabolismo , Glândulas Mamárias Animais/crescimento & desenvolvimento , Glândulas Mamárias Animais/metabolismo , Camundongos Transgênicos , Modelos Biológicos , Ligação ProteicaRESUMO
Tremendous progress has been made in the field of stem cell biology. This is in part due to the emergence of various vertebrate organs, including the mammary gland, as an amenable model system for adult stem cell studies and remarkable technical advances in single cell technology and modern genetic lineage tracing. In the current review, we summarize the recent progress in mammary gland stem cell biology at both the adult and embryonic stages. We discuss current challenges and controversies, and potentially new and exciting directions for future research. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration.