BMP Receptor ALK3 Controls Collecting System Development
Open Access
- 1 January 2008
- journal article
- Published by Wolters Kluwer Health in Journal of the American Society of Nephrology
- Vol. 19 (1), 117-124
- https://doi.org/10.1681/asn.2007010080
Abstract
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 (Alk3UB−/− mice). At the onset of branching morphogenesis, Alk3UB−/− kidneys are characterized by an abnormal primary (1°) ureteric bud branch pattern and an increased number of ureteric bud branches. However, during later stages of renal development, Alk3UB−/− kidneys have fewer ureteric bud branches and collecting ducts than wild-type kidneys. Postnatal Alk3UB−/− mice exhibit a dysplastic renal phenotype characterized by hypoplasia of the renal medulla, a decreased number of medullary collecting ducts, and abnormal expression of β-catenin and c-MYC in medullary tubules. In summary, normal kidney development requires ALK3-dependent BMP signaling, which controls ureteric bud branching.Keywords
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