MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London, UK.
Development. 2010 Feb;137(4):641-50. doi: 10.1242/dev.041913.
Crumbs (Crb) is a conserved apical polarity determinant required for zonula adherens specification and remodelling during Drosophila development. Interestingly, crb function in maintaining apicobasal polarity appears largely dispensable in primary epithelia such as the imaginal discs. Here, we show that crb function is not required for maintaining epithelial integrity during the morphogenesis of the Drosophila head and eye. However, although crb mutant heads are properly developed, they are also significantly larger than their wild-type counterparts. We demonstrate that in the eye, this is caused by an increase in cell proliferation that can be attributed to an increase in ligand-dependent Notch (N) signalling. Moreover, we show that in crb mutant cells, ectopic N activity correlates with an increase in N and Delta endocytosis. These data indicate a role for Crb in modulating endocytosis at the apical epithelial plasma membrane, which we demonstrate is independent of Crb function in apicobasal polarity. Overall, our work reveals a novel function for Crb in limiting ligand-dependent transactivation of the N receptor at the epithelial cell membrane.
crumbs (Crb) 是一个保守的顶端极性决定因素，在果蝇发育过程中需要用于粘着连接的规范和重塑。有趣的是，Crb 在维持初级上皮细胞（如 imaginal discs）的顶端-基底极性中的功能似乎很大程度上是可有可无的。在这里，我们表明，在果蝇头部和眼睛的形态发生过程中，Crb 的功能对于维持上皮完整性并不是必需的。然而，尽管 crb 突变体头部发育正常，但它们也比其野生型对应物明显更大。我们证明，在眼睛中，这是由于细胞增殖增加所致，这可归因于配体依赖性 Notch (N) 信号的增加。此外，我们表明在 crb 突变体细胞中，异位 N 活性与 N 和 Delta 内吞作用的增加相关。这些数据表明 Crb 在调节顶端上皮质膜的内吞作用方面具有作用，我们证明这与 Crb 在顶端-基底极性中的功能无关。总的来说，我们的工作揭示了 Crb 在限制上皮细胞膜上 N 受体的配体依赖性转激活中的新功能。
