Detailseite
Projekt
The role of nephronophtisis proteins in motile cilia and renal tubules of Xenopus laevis
Antragsteller
Dr. Soeren Lienkamp
Fachliche Zuordnung
Nephrologie
Förderung
Förderung von 2008 bis 2015
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 58488057
The renal manifestations of nephronophthisis (NPH) are often part of a complex syndrome, affecting multiple organs and tissues. Most gene products mutated in nephronophthisis (nephrocystins, NPHPs) localize to the cilium, a microtubular organelle attached to most body cells. Hence it has been postulated that a dysfunction of the cilium causes the cystic kidney disease and extrarenal manifestations of NPHP. NPHPs are also required for planar cell polarity signalling (PCP); however the link between cilia and the PCP signalling pathway is still poorly understood. Cilia are positioned in a highly polarized manner in some tissues. This proposal will elucidate the role of NPHPs in ciliary polarization and PCP signalling, using the Xenopus laevis animal model. Focusing on the polarization of multi-ciliated Xenopus epidermal cells, the structural integrity, motility, and anchoring of cilia at the apical membrane as well as the crosstalk with the PCP pathway will be analyzed in detail. Since renal tubules are specified in a proximal-to-distal fashion, the Xenopus pronephros model will be utilized to determine, if single tubular epithelial cells exhibit features of an anterlor-to-posterior polarization, and if the planar polarity of tubule cells is mediated by NPHPs. The results will provide further insight in the molecular function of NPHPs, and a framework to understand their role in mammalian organ development and homeostasis.
DFG-Verfahren
Klinische Forschungsgruppen
