Isabella Adam J, Horne-Badovinac Sally
Committee on Development, Regeneration and Stem Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
Committee on Development, Regeneration and Stem Cell Biology, The University of Chicago, Chicago, IL 60637, USA; Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
Dev Cell. 2016 Jul 11;38(1):47-60. doi: 10.1016/j.devcel.2016.06.009.
Basement membranes (BMs) are planar protein networks that support epithelial function. Regulated changes to BM architecture can also contribute to tissue morphogenesis, but how epithelia dynamically remodel their BMs is unknown. In Drosophila, elongation of the initially spherical egg chamber correlates with the generation of a polarized network of fibrils in its surrounding BM. Here, we use live imaging and genetic manipulations to determine how these fibrils form. BM fibrils are assembled from newly synthesized proteins in the pericellular spaces between the egg chamber's epithelial cells and undergo oriented insertion into the BM by directed epithelial migration. We find that a Rab10-based secretion pathway promotes pericellular BM protein accumulation and fibril formation. Finally, by manipulating this pathway, we show that BM fibrillar structure influences egg chamber morphogenesis. This work highlights how regulated protein secretion can synergize with tissue movement to build a polarized BM architecture that controls tissue shape.
基底膜(BMs)是支持上皮功能的平面蛋白质网络。对BM结构的调控性变化也有助于组织形态发生,但上皮细胞如何动态重塑其BM尚不清楚。在果蝇中,最初呈球形的卵室的伸长与其周围BM中极化的纤维网络的形成相关。在这里,我们使用实时成像和基因操作来确定这些纤维是如何形成的。BM纤维由卵室上皮细胞之间的细胞周间隙中新合成的蛋白质组装而成,并通过上皮细胞的定向迁移进行定向插入到BM中。我们发现基于Rab10的分泌途径促进细胞周BM蛋白积累和纤维形成。最后,通过操纵该途径,我们表明BM纤维结构影响卵室形态发生。这项工作突出了调控性蛋白质分泌如何与组织运动协同作用,以构建控制组织形状的极化BM结构。