QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online December 22, 2008
doi: 10.1242/10.1242/dev.024463

This Article Figures Only Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ishibe, S. Articles by Cantley, L. G. Search for Related Content PubMed Articles by Ishibe, S. Articles by Cantley, L. G. Social Bookmarking                         What's this?

Met and the epidermal growth factor receptor act cooperatively to regulate final nephron number and maintain collecting duct morphology

¹ Section of Nephrology, Yale University School of Medicine, New Haven, CT 06510, USA.
² Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
³ Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁴ Department of Nephrology, Hannover Medical School, Hannover, Germany.

^* Authors for correspondence (e-mail: shuta.ishibe{at}yale.edu and lloyd.cantley{at}yale.edu)

Accepted 9 November 2008

Ureteric bud (UB) branching during kidney development determines the final number of nephrons. Although hepatocyte growth factor and its receptor Met have been shown to stimulate branching morphogenesis in explanted embryonic kidneys, loss of Met expression is lethal during early embryogenesis without obvious kidney abnormalities. Met^fl/fl;HoxB7-Cre mice, which lack Met expression selectively in the UB, were generated and found to have a reduction in final nephron number. These mice have increased Egf receptor expression in both the embryonic and adult kidney, and exogenous Egf can partially rescue the branching defect seen in kidney explants. Met^fl/fl;HoxB7-Cre;wa-2/wa-2 mice, which lack normal Egfr and Met signaling, exhibit small kidneys with a marked decrease in UB branching at E14.5 as well as a reduction in final glomerular number. These mice developed progressive interstitial fibrosis surrounding collecting ducts with kidney failure and death by 3-4 weeks of age. Thus, in support of previous in vitro findings, Met and the Egf receptor can act cooperatively to regulate UB branching and mediate maintenance of the normal adult collecting duct.

Key words: Kidney, Met receptor, Ureteric bud, Branching, Mouse

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				G. R. Dressler Advances in early kidney specification, development and patterning Development, December 1, 2009; 136(23): 3863 - 3874. [Abstract] [Full Text] [PDF]

				Z. Gai, G. Zhou, S. Itoh, Y. Morimoto, H. Tanishima, I. Hatamura, K. Uetani, M. Ito, and Y. Muragaki Trps1 Functions Downstream of Bmp7 in Kidney Development J. Am. Soc. Nephrol., November 1, 2009; 20(11): 2403 - 2411. [Abstract] [Full Text] [PDF]

				M. M. Shah, J. B. Tee, T. Meyer, C. Meyer-Schwesinger, Y. Choi, D. E. Sweeney, T. F. Gallegos, K. Johkura, E. Rosines, V. Kouznetsova, et al. The instructive role of metanephric mesenchyme in ureteric bud patterning, sculpting, and maturation and its potential ability to buffer ureteric bud branching defects Am J Physiol Renal Physiol, November 1, 2009; 297(5): F1330 - F1341. [Abstract] [Full Text] [PDF]

				Y. Liu, N. Chattopadhyay, S. Qin, C. Szekeres, T. Vasylyeva, Z. X. Mahoney, M. Taglienti, C. M. Bates, H. A. Chapman, J. H. Miner, et al. Coordinate integrin and c-Met signaling regulate Wnt gene expression during epithelial morphogenesis Development, March 1, 2009; 136(5): 843 - 853. [Abstract] [Full Text] [PDF]