BMP receptor ALK3 controls collecting system development

Journal of the American Society of Nephrology : JASN
Sunny HartwigNorman D Rosenblum

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 (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.

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Citations

Oct 30, 2008·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Ihor V Yosypiv
Dec 17, 2008·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Darren Bridgewater, Norman D Rosenblum
Mar 5, 2011·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Leif OxburghBeth Hill
May 3, 2011·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Jing Yu
Aug 14, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Mariusz KaczmarczykAndrzej Ciechanowicz
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Feb 4, 2012·American Journal of Physiology. Renal Physiology·Renfang SongIhor V Yosypiv
Feb 23, 2011·The Journal of Clinical Investigation·Jason E CainNorman D Rosenblum
Sep 20, 2008·BMC Developmental Biology·Ulrika BlankLeif Oxburgh
Apr 10, 2009·Journal of the American Society of Nephrology : JASN·Barry W LarmanLeif Oxburgh
Oct 17, 2009·Journal of the American Society of Nephrology : JASN·Sunder Sims-LucasCarlton M Bates
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