2046-2530-1-S1-P79 2046-2530 Poster presentation <p>Functional analysis of the transition zone protein Rpgrip1l during zebrafish development</p> VesqueCchristine.vesque@snv.jussieu.fr MahuzierA AnselmeI Leroux-BergerM Schneider-MaunourySJ

UMR 7622 CNRS, ERL INSERM 969, Université P. et M. Curie, France

Cilia <p>Proceedings of the First International Cilia in Development and Disease Scientific Conference (2012) </p>Phil L Beales and Hannah M MitchisonThis supplement has not been supported by sponsorship or other external funding.Meeting abstracts<p>First International Cilia in Development and Disease Scientific Conference (2012)</p>London, UK16-18 May 2012http://www.ciliopathyalliance.org/2046-2530 2012 1 Suppl 1 P79 http://www.ciliajournal.com/content/1/S1/P79 10.1186/2046-2530-1-S1-P79
16112012 2012Vesque et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

We investigated the function of Rpgrip1l during zebrafish development. Rpgrip1l encodes a protein localised at the ciliary transition zone and interacts functionally with NPH and MKS for the formation and function of the ciliary gate. The human RPGRIP1L gene is a causal gene in Meckel and Joubert type B syndromes, characterised by polydactyly, kidney cysts and central nervous system malformations. Using morpholinos injection, we show that loss of Rpgrip1l function leads to several early phenotypes such as convergent-extension phenotype, randomisation of left-right asymmetry and hydrocephaly. We focussed our study on the Wnt-PCP defects and we demonstrated that in the zebrafish floorplate, Rpgrip1l is required for correct positioning of the basal body along the planar polarity axis. We confirmed Rpgrip1l function on basal body positioning in the mechanosensory hair cells of the cochlea of the murine mutant for Rpgrip1l. Our results strongly suggest that Rpgrip1l is essential for recruiting and stabilizing dishevelled, a major actor of the PCP pathway, at the basal body and/or cilium. Indeed, in two different cell types, in the zebrafish floor plate and in the murine cochlea, dishevelled proteins are enriched at the cilium and/or basal body, and this localization is severely perturbed upon Rpgrip1l depletion. Finally, we demonstrate that, in the zebrafish floor plate, the function of Rpgrip1l in basal body positioning is mediated by dishevelled. We propose that Rpgrip1l participates in a protein complex required for recruiting and stabilizing dishevelled at the cilium, a process essential for planar polarization of the basal body.