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First published online 26 August 2009
doi: 10.1242/dev.036269

Development 136, 3357-3366 (2009)
Published by The Company of Biologists 2009
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β1 integrin is necessary for ureteric bud branching morphogenesis and maintenance of collecting duct structural integrity

Xi Zhang1,2, Glenda Mernaugh1, Dong-Hua Yang3, Leslie Gewin1, Manakan B. Srichai1,4, Raymond C. Harris1,5, Juan M. Iturregui6, Raoul D. Nelson7, Donald E. Kohan7, Dale Abrahamson8, Reinhard Fässler9, Peter Yurchenco3, Ambra Pozzi1,2,4 and Roy Zent1,2,4,5,*

1 Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
2 Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
3 Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
4 Department of Medicine, Veterans Affairs Hospital, Nashville, TN 037212, USA.
5 Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
6 Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
7 Division of Nephrology, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
8 Department of Anatomy and Cell Biology, University of Kansas Medical Center, KS 66160, USA.
9 Max-Planck Institute of Biochemistry, Department of Molecular Medicine, Am Klopferspitz 18, 82152 Martinsried, Germany.

* Author for correspondence (roy.zent{at}vanderbilt.edu)

Accepted 30 July 2009

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.

Key words: Kidney, Growth factor receptors, Renal development, Branching morphogenesis, Mouse


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