title: beta1 integrin is necessary for ureteric bud branching morphogenesis and maintenance of collecting duct structural integrity.
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 beta1 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. beta1 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 beta1-null UBs in vivo. Thus beta1 integrins can regulate organ branching morphogenesis during development by mediating growth-factor-dependent signaling in addition to their well-defined role as adhesion receptors.
authors.affiliation: Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Glenda
authors.initials: G
authors.lastname: Mernaugh
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Yang
authors.forename: Leslie
authors.initials: L
authors.lastname: Gewin
authors.forename: Manakan B
authors.initials: MB
authors.lastname: Srichai
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Harris
authors.forename: Juan M
authors.initials: JM
authors.lastname: Iturregui
authors.forename: Raoul D
authors.initials: RD
authors.lastname: Nelson
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
authors.forename: Dale
authors.initials: D
authors.lastname: Abrahamson
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Peter
authors.initials: P
authors.lastname: Yurchenco
authors.forename: Ambra
authors.initials: A
authors.lastname: Pozzi
authors.forename: Roy
authors.initials: R
authors.lastname: Zent
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006133:Growth Substances / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis; D009924:Organ Culture Techniques; D015398:Signal Transduction; D014513:Ureter / Q000196:embryology* / Q000378:metabolism*
chemical_list: D006133:Growth Substances; D019012:Integrin beta1