beta1 integrin is necessary for ureteric bud branching morphogenesis and maintenance of collecting duct structural integrity.
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.
Zhang
Xi
X
Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Mernaugh
Glenda
G
Yang
Dong-Hua
DH
Gewin
Leslie
L
Srichai
Manakan B
MB
Harris
Raymond C
RC
Iturregui
Juan M
JM
Nelson
Raoul D
RD
Kohan
Donald E
DE
Abrahamson
Dale
D
Fässler
Reinhard
R
Yurchenco
Peter
P
Pozzi
Ambra
A
Zent
Roy
R
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*
D006133:Growth Substances; D019012:Integrin beta1