Apical secrection and assembly of extracellular matrix during Drosophila oogenesis

细胞外基质的极化分泌和组装是细胞和生物体功能的重要基础过程。然而，很少有人知道这些矩阵是如何组装在体内。果蝇卵壳是由极化的上皮滤泡细胞分泌的一种特殊的细胞外基质，是分析细胞外基质在体内组装的一个很好的模型系统。我们最近发现了果蝇基因cad99C的突变，并提供了几条证据，证明这些突变体在形成适当的蛋壳方面有缺陷。Cad99C是人原钙粘蛋白15的果蝇直系同源物，原钙粘蛋白15是Ca2+依赖性细胞粘附分子家族的蛋白质，其在病因学上与耳聋（I型Usher综合征）相关。该项目的目的是通过分子和生物化学方法以及超微结构分析的结合来确定Cad99C如何有助于果蝇蛋壳的形成。预计我们的分析将提供新的见解极化细胞顶端分泌和组装细胞外基质的机制，此外，到Usher综合征I型的分子和细胞生物学基础。

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.