Peptides from the PKD repeats of polycystin, the PKD1 gene product, modulate pattern formation in the developing kidney.
Mutations in the PKD1 gene cause the majority of cases of autosomal dominant polycystic kidney disease. The PKD1 gene codes for a protein of unknown function, polycystin-1, that is predicted to be a receptor. Its large extracellular domain contains 16 copies of novel motif, the PKD repeat, that is likely to be a ligand binding domain based on its similarity to immunoglobulin domains. These observations suggested that soluble fragments of the extracellular domain of polycystin-1 could be used as competitive inhibitors of polycystin function in a suitable model system. Polycystin-1 is highly expressed in the ureteric bud and other branching epithelia during development and interacts with beta-catenin, a molecule known to play a role in branching morphogenesis. These data suggested that polycystin-1 might play a role in branching morphogenesis. I show here that peptides derived from the PKD repeats of polycystin-1 caused an asymmetric pattern of ureteric bud branching in cultured kidney rudiments. Treatment of kidney rudiments with experimental but not control peptides reduced both the number of ureteric bud branches and the number of nephrons. Experimental peptides produced significant morphogenetic effects at concentrations < or = 0.1 mM. These data suggest that polycystin-1 plays a role in branching morphogenesis by the ureteric bud.
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D005399:Fishes; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology; D016891:Polycystic Kidney, Autosomal Dominant / Q000196:embryology / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D050396:TRPP Cation Channels