Apical secrection and assembly of extracellular matrix during Drosophila oogenesis

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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.