Peptides from the PKD repeats of polycystin, the PKD1 gene product, modulate pattern formation in the developing kidney

Mutations in the PKD T gene cause the majority of cases of autosomal domina nt polycystic kidney disease. The PKD 1 gene codes for a protein of unknown function, polycystin-1, that is predicted to be a receptor. its large extr acellular domain contains 16 copies of novel motif, the PKD repeat, that is likely to be a nd binding domain based on its similarity to immunoglobulin domains. These observations suggested that soluble fragments of the extrac ellular domain of polycystin-1 could be used as competitive inhibitors of p olycystin function in a suitable model system. Polycystin-1 is highly expre ssed in the ureteric bud branching epithelia during development and interac ts with beta-catenin, a molecule known to play a role in branching morphoge nesis. These data suggested that polycystin-1 might play a role in branchin g morphogenesis. show here that peptides derived from the PKD repeats of po lycystin-1 caused an asymmetric pattern of ureteric bud branching in cultur ed kidney rudiments. Treatment of kidney rudiments with experimental but no t control peptides reduced both the number of ureteric bud branches and the number of nephrons. Experimental peptides produced significant morphogenet ic effects at concentrations less than or equal to 0.1 mM. These data sugge st that polycystin-1 plays a role in branching morphogenesis by the ureteri c bud. (C) 1999 Wiley-Liss, Inc.