Inhibitory BMO signaling controls mammalian renal branching morphogenesis in vivo
By: Sunny Sun-Hee Hartwig.
Published: 2006
Language: eng
Number of pages: 157
ISBN-13: 9780494159293
Description: In this thesis I investigated the role of the inhibitory Bmp  signaling pathway during mouse kidney renal development using (i) genetic haploinsufficiency models to investigate the functions of Bmp2 and Gpc3-Bmp2 interactions during renal development  in vivo and (ii) conditional Alk3 loss-of-function in the UB lineage to investigate the function of Alk3-dependent  Bmp signaling during RBM in vivo.During embryonic development, the collecting duct system of the kidney arises through iterative growth and branching of the ureteric bud (UB) and daughter collecting ducts, a process termed renal branching morphogenesis (RBM). Previous work in our lab identified an inhibitory ALK3-dependent BMP signaling pathway that controls cellular and morphogenetic events during RBM  in vitro and in transgenic over-expression mouse models. However, the early embryonic lethality of homozygous Bmp2-/- and Alk3-/- mice has precluded complementary conventional loss-of-function studies to define the role of Bmp signaling during renal development in vivo.Results from this thesis provide the first genetic evidence that an inhibitory  Bmp2 signaling pathway controls UB cell proliferation and branching during RBM in vivo, and that Bmp2 signaling is genetically modulated by Gpc3. Further, these results demonstrate an essential requirement of ALK3-dependent Bmp  signaling for normal kidney development in vivo, and identify a critical architectural role for ALK3 in establishing and maintaining the primary UB branching pattern.
Notes: Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3531.

Thesis (Ph.D.)--University of Toronto, 2006.

Includes bibliographic references.

Electronic version licensed for access by U. of T. users.