BMP receptor ALK3 controls collecting system development.
The molecular signals that regulate growth and branching of the ureteric bud during formation of the renal collecting system are largely undefined. Members of the bone morphogenetic protein (BMP) family signal through the type I BMP receptor ALK3 to inhibit ureteric bud and collecting duct cell morphogenesis in vitro. We investigated the function of the BMP signaling pathway in vivo by generating a murine model of ALK3 deficiency restricted to the ureteric bud lineage (Alk3(UB-/-) mice). At the onset of branching morphogenesis, Alk3(UB-/-) kidneys are characterized by an abnormal primary (1 degrees ) ureteric bud branch pattern and an increased number of ureteric bud branches. However, during later stages of renal development, Alk3(UB-/-) kidneys have fewer ureteric bud branches and collecting ducts than wild-type kidneys. Postnatal Alk3(UB-/-) mice exhibit a dysplastic renal phenotype characterized by hypoplasia of the renal medulla, a decreased number of medullary collecting ducts, and abnormal expression of beta-catenin and c-MYC in medullary tubules. In summary, normal kidney development requires ALK3-dependent BMP signaling, which controls ureteric bud branching.
Hartwig
Sunny
S
Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada.
Bridgewater
Darren
D
Di Giovanni
Valeria
V
Cain
Jason
J
Mishina
Yuji
Y
Rosenblum
Norman D
ND
D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000502:physiology*; D047108:Embryonic Development; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D007668:Kidney / Q000196:embryology; D007685:Kidney Tubules, Collecting / Q000196:embryology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014513:Ureter / Q000196:embryology / Q000502:physiology
D049452:Green Fluorescent Proteins; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I