H-Ras, R-Ras, and TC21 differentially regulate ureteric bud cell branching morphogenesis

Ambra Pozzi, Sergio Coffa, Nada Bulus, Wenqin Zhu, Dong Chen, Xiwu Chen, Glenda Mernaugh, Yan Su, Songmin Cai, Amar Singh, Marcela Brissova, Roy Zent

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17 Scopus citations

Abstract

The collecting system of the kidney, derived from the ureteric bud (UB), undergoes repetitive bifid branching events during early development followed by a phase of tubular growth and elongation. Although members of the Ras GTPase family control cell growth, differentiation, proliferation, and migration, their role in development of the collecting system of the kidney is unexplored. In this study, we demonstrate that members of the R-Ras family of proteins, R-Ras and TC21, are expressed in the murine collecting system at E13.5, whereas H-Ras is only detected at day E17.5. Using murine UB cells expressing activated H-Ras, R-Ras, and TC21, we demonstrate that R-Ras-expressing cells show increased branching morphogenesis and cell growth, TC21-expressing cells branch excessively but lose their ability to migrate, whereas H-Ras-expressing cells migrated the most and formed long unbranched tubules. These differences in branching morphogenesis are mediated by differential regulation/activation of the Rho family of GTPases and mitogen-activated protein kinases. Because most branching of the UB occurs early in development, it is conceivable that R-Ras and TC-21 play a role in facilitating branching and growth in early UB development, whereas H-Ras might favor cell migration and elongation of tubules, events that occur later in development.

Original languageEnglish (US)
Pages (from-to)2046-2056
Number of pages11
JournalMolecular biology of the cell
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2006

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Pozzi, A., Coffa, S., Bulus, N., Zhu, W., Chen, D., Chen, X., Mernaugh, G., Su, Y., Cai, S., Singh, A., Brissova, M., & Zent, R. (2006). H-Ras, R-Ras, and TC21 differentially regulate ureteric bud cell branching morphogenesis. Molecular biology of the cell, 17(4), 2046-2056. https://doi.org/10.1091/mbc.E05-08-0800