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Numb regulates cell tension required for mammary duct elongation

机译：麻木调节乳腺导管伸长所需的细胞张力

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摘要

The mammary gland undergoes extensive expansion of a ductal network through the stroma during puberty and is an excellent model for understanding epithelial tube morphogenesis. To investigate a role for Numb, a multifaceted adapter protein, in epithelial tube morphogenesis, we conditionally deleted it from the mammary epithelium. We report that Numb-depletion results in altered extracellular-matrix organization, reduced cell tension, altered cell shape, and increased cell packing density, which results in a 50% reduction in mammary duct elongation. Using laser ablationin vitroand geometric-based cell force inferencein vivo, we determined that Numb-deficient cells have altered cortical tension. Duct elongation defects were associated with altered E-cadherin distribution, but were independent of proliferation, apoptosis in ducts or end buds. This highlights a critical role for Numb in a mechanical mechanism that is required to maintain cell packing density during epithelial tube elongation.
机译：乳腺在青春期期间会通过基质广泛地扩张导管网络，并且是了解上皮管形态发生的极好模型。为了研究Numb（一种多面体衔接蛋白）在上皮管形态发生中的作用，我们有条件地将其从乳腺上皮中删除。我们报告Numb耗竭导致改变的细胞外基质组织，减少的细胞张力，改变的细胞形状，并增加细胞堆积密度，从而导致乳腺导管伸长率降低50％。使用体外激光消融和体内基于几何的细胞力推论，我们确定Numb缺陷细胞改变了皮质张力。导管伸长缺陷与E-钙粘蛋白分布改变有关，但与增殖或导管或末梢芽的凋亡无关。这突显了Numb在上皮管延长过程中维持细胞堆积密度所需的机械机制中的关键作用。

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