Apical secrection and assembly of extracellular matrix during Drosophila oogenesis

细胞外基质的极化分泌和组装是重要的细胞和生物功能的基本过程。然而，人们对这些基质是如何在体内组装的知之甚少。果蝇蛋壳是一种特殊的细胞外基质，由极化的上皮毛囊细胞分泌，是分析体内细胞外基质组装的良好模型系统。我们最近发现了果蝇基因cad99C的突变，并提供了几条证据表明这些突变在形成合适的蛋壳方面存在缺陷。Cad99C是果蝇对人类原钙粘附素15的同源基因，原钙粘附素15是一种钙依赖细胞黏附分子家族的蛋白质，在病因上与耳聋(Usher综合征I型)有关。拟议项目的目的是通过结合分子和生化方法以及超微结构分析来确定Cad99C如何对果蝇蛋壳的形成起到作用。预计我们的分析将为极化细胞顶端分泌和组装细胞外基质的机制提供新的见解，此外，还将为I型Usher综合征的分子和细胞生物学基础提供新的见解。

The polarized secretion and assembly of extracellular matrices are fundamental processes important for cellular and organismal function. However, little is known how these matrices are assembled in vivo. The Drosophila eggshell is a specialized extracellular matrix secreted by polarized epithelial follicle cells and has served as an excellent model system to analyze extracellular matrix assembly in vivo. We have recently identified mutations in the Drosophila gene cad99C and provide several lines of evidence that these mutants are defective in forming a proper eggshell. Cad99C is the Drosophila ortholog of human Protocadherin 15, a protein of the family of Ca2+- dependent cell adhesion molecules that is etiologically associated with deafness (Usher syndrome type I). The aim of the proposed project is to determine by a combination of molecular and biochemical approaches as well as ultra-structural analysis how Cad99C contributes to the formation of the Drosophila eggshell. It is expected that our analysis will provide novel insights into mechanisms used by polarized cells to apically secrete and assemble extracellular matrices and, in addition, into the molecular and cell biological basis of Usher syndrome type I.