Project Details
Projekt
Cyst formation in zebrafish
Applicant
Dr. Albrecht Kramer-Zucker
Subject Area
Nephrology
Term
from 2008 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 58488057
Polycystic kidney disease is a systemic disease and regarded as ciliopathy. How ciliary dysfunction is causing the different organ manifestations is still not fully understood. Increased cell proliferation and also apoptosis, disturbed cell polarity and tissue repair mechanisms seem to lead to disrupted tubular geometry. We will investigate ELMO1 (Engulfment and cell motility protein 1), a new cyst candidate protein, that was originally discovered in C. elegans in regulating apoptosis and cell migration and that functions together with Dock180 as a Rac-GEF. Our preliminary results show that ELMO1 and Dock180 share localization to the cilium and basal body with other known cyst proteins. Knockdown of ELMO1 by morpholino injection led to cyst formation in zebrafish pronephros. This raises the hypothesis that ELMO1/Dock180 are involved in signalling pathways that are implicated in cyst formation. To test this hypothesis the function of ELMO1 will be studied in vivo by overexpression and morpholino-knockdown experiments. The resulting phenotypes will be evaluated for cilia structure and motility, cell polarity, and fluid flow in the pronephric duct. In addition, transgenic fish lines expressing GFP fusion proteins under the control of pronephros specific promoters will be utilized to try to understand how tubular geometry is disrupted in cystic kidney disease. Studies on kidney regeneration after photoablation of pronephric epithelial tube cells in wild-type and cystic kidney background will be performed to gain further insight into maintenance of tubular geometry.
DFG Programme
Clinical Research Units
