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First published online 31 January 2007
doi: 10.1242/dev.02776

Development 134, 921-931 (2007)
Published by The Company of Biologists 2007
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New functions for a vertebrate Rho guanine nucleotide exchange factor in ciliated epithelia

Jennifer R. Panizzi1, Jason R. Jessen2, Iain A. Drummond3 and Lilianna Solnica-Krezel1,*

1 Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.
2 Department of Medicine, Vanderbilt University Medical School, Nashville, TN 37232, USA.
3 Nephrology Division, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA 02129, USA.

* Author for correspondence (e-mail: lilianna.solnica-krezel{at}vanderbilt.edu)

Accepted 6 December 2006

Human ARHGEF11, a PDZ-domain-containing Rho guanine nucleotide exchange factor (RhoGEF), has been studied primarily in tissue culture, where it exhibits transforming ability, associates with and modulates the actin cytoskeleton, regulates neurite outgrowth, and mediates activation of Rho in response to stimulation by activated G{alpha}12/13 or Plexin B1. The fruit fly homolog, RhoGEF2, interacts with heterotrimeric G protein subunits to activate Rho, associates with microtubules, and is required during gastrulation for cell shape changes that mediate epithelial folding. Here, we report functional characterization of a zebrafish homolog of ARHGEF11 that is expressed ubiquitously at blastula and gastrula stages and is enriched in neural tissues and the pronephros during later embryogenesis. Similar to its human homolog, zebrafish Arhgef11 stimulated actin stress fiber formation in cultured cells, whereas overexpression in the embryo of either the zebrafish or human protein impaired gastrulation movements. Loss-of-function experiments utilizing a chromosomal deletion that encompasses the arhgef11 locus, and antisense morpholino oligonucleotides designed to block either translation or splicing, produced embryos with ventrally-curved axes and a number of other phenotypes associated with ciliated epithelia. Arhgef11-deficient embryos often exhibited altered expression of laterality markers, enlarged brain ventricles, kidney cysts, and an excess number of otoliths in the otic vesicles. Although cilia formed and were motile in these embryos, polarized distribution of F-actin and Na+/K+-ATPase in the pronephric ducts was disturbed. Our studies in zebrafish embryos have identified new, essential roles for this RhoGEF in ciliated epithelia during vertebrate development.

Key words: Pronephros, Left-right asymmetry, Otoliths, PDZ-RhoGEF, Arhgef11, Cell polarity, Zebrafish


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New developmental roles for RhoGEFs?

Development 2007 134: e505. [Full Text]  



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