Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06519, USA.
Dev Cell. 2011 Aug 16;21(2):245-56. doi: 10.1016/j.devcel.2011.06.026.
Basement membranes (BMs) are resilient polymer structures that surround organs in all animals. Tissues, however, undergo extensive morphological changes during development. It is not known whether the assembly of BM components plays an active morphogenetic role. To study in vivo the biogenesis and assembly of Collagen IV, the main constituent of BMs, we used a GFP-based RNAi method (iGFPi) designed to knock down any GFP-trapped protein in Drosophila. We found with this method that Collagen IV is synthesized by the fat body, secreted to the hemolymph (insect blood), and continuously incorporated into the BMs of the larva. We also show that incorporation of Collagen IV determines organ shape, first by mechanically constricting cells and second through recruitment of Perlecan, which counters constriction by Collagen IV. Our results uncover incorporation of Collagen IV and Perlecan into BMs as a major determinant of organ shape and animal form.
基底膜(BMs)是一种有弹性的聚合物结构,存在于所有动物的器官周围。然而,组织在发育过程中会经历广泛的形态变化。目前尚不清楚 BM 成分的组装是否发挥了积极的形态发生作用。为了研究体内 Collagen IV(BM 的主要成分)的生物发生和组装,我们使用了一种基于 GFP 的 RNAi 方法(iGFPi),该方法旨在敲低果蝇中任何 GFP 捕获的蛋白质。我们用这种方法发现 Collagen IV 是由血体(昆虫血液)合成的,分泌到血淋巴中,并不断掺入幼虫的 BM 中。我们还表明,Collagen IV 的掺入决定了器官的形状,首先是通过机械地收缩细胞,其次是通过招募 Perlecan,后者通过 Collagen IV 对抗收缩。我们的结果揭示了 Collagen IV 和 Perlecan 掺入 BM 作为器官形状和动物形态的主要决定因素。