β1 Integrin is necessary for ureteric bud branching morphogenesis and maintenance of collecting duct structural integrity

Xi Zhang, Glenda Mernaugh, Dong Hua Yang, Leslie Gewin, Manakan B. Srichai, Raymond C. Harris, Juan M. Iturregui, Raoul D. Nelson, Donald E. Kohan, Dale Abrahamson, Reinhard Fässler, Peter Yurchenco, Ambra Pozzi, Roy Zent

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

The kidney collecting system develops from branching morphogenesis of the ureteric bud (UB). This process requires signaling by growth factors such as glial cell line derived neurotrophic factor (GDNF) and fibroblast growth factors (FGFs) as well as cell extracellular matrix interactions mediated by integrins. The importance of integrin signaling in UB development was investigated by deleting integrin β1 at initiation (E10.5) and late (E18.5) stages of development. Deletion at E10.5 resulted in a severe branching morphogenesis phenotype. Deletion at E18.5 did not alter renal development but predisposed the collecting system to severe injury following ureteric obstruction. β1 integrin was required for renal tubular epithelial cells to mediate GDNF- and FGF-dependent signaling despite normal receptor localization and activation in vitro. Aberrations in the same signaling molecules were present in the β1-null UBs in vivo. Thus β1 integrins can regulate organ branching morphogenesis during development by mediating growth-factor-dependent signaling in addition to their well-defined role as adhesion receptors.

Original languageEnglish
Pages (from-to)3357-3366
Number of pages10
JournalDevelopment
Volume136
Issue number19
DOIs
StatePublished - Oct 1 2009

Keywords

  • Branching morphogenesis
  • Growth factor receptors
  • Kidney
  • Mouse
  • Renal development

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