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First published online 28 January 2009
doi: 10.1242/dev.027805

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Coordinate integrin and c-Met signaling regulate Wnt gene expression during epithelial morphogenesis

Yingjie Liu^1,*,, Nibedita Chattopadhyay^1,*,, Shan Qin^1,*, Charles Szekeres^1,, Tetyana Vasylyeva¹, Zhen X. Mahoney², Mary Taglienti¹, Carlton M. Bates³, Harold A. Chapman⁴, Jeffrey H. Miner² and Jordan A. Kreidberg^1,¶

¹ Department of Medicine, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA, and Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
² Renal Division, Washington University School of Medicine, St Louis, MO 63110, USA.
³ Center for Cell and Developmental Biology, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.
⁴ Cardiovascular Research Institute, University of California San Francisco, 513 Parnassus Avenue, HSE-201 San Francisco, CA 94143-0130, USA.

^¶ Author for correspondence (e-mail: Jordan.Kreidberg{at}childrens.harvard.edu)

Accepted 18 December 2008

Integrin receptors for the extracellular matrix and receptor tyrosine kinase growth factor receptors represent two of the major families of receptors that transduce into cells information about the surrounding environment. Wnt proteins are a major family of signaling molecules that regulate morphogenetic events. There is presently little understanding of how the expression of Wnt genes themselves is regulated. In this study, we demonstrate that 3β1 integrin, a major laminin receptor involved in the development of the kidney, and c-Met, the receptor for hepatocyte growth factor, signal coordinately to regulate the expression of Wnt7b in the mouse. Wnt signals in turn appear to regulate epithelial cell survival in the papilla of the developing kidney, allowing for the elongation of epithelial tubules to form a mature papilla. Together, these results demonstrate how signals from integrins and growth factor receptors can be integrated to regulate the expression of an important family of signaling molecules so as to regulate morphogenetic events.

Key words: Integrins, Signal transduction, Wnt genes, Receptor tyrosine kinase

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