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First published online 20 August 2003
doi: 10.1242/dev.00698


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Development 130, 4847-4858 (2003)
Copyright © 2003 The Company of Biologists Limited

Fusicoccin signaling reveals 14-3-3 protein function as a novel step in left-right patterning during amphibian embryogenesis

Tom D. Bunney1,*, Albertus H. De Boer1 and Michael Levin2,{dagger}

1 Vrije Universiteit, Faculty of Earth and Life Sciences, Department of Developmental Genetics, Section Molecular Plant Physiology and Biophysics, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands
2 Department of Cytokine Biology, The Forsyth Institute, 140 The Fenway, and Department of Developmental and Craniofacial Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA

{dagger} Author for correspondence (e-mail: mlevin{at}forsyth.org)

Accepted 1 July 2003

To gain insight into the molecular mechanisms underlying the control of morphogenetic signals by H+ flux during embryogenesis, we tested Fusicoccin-A (FC), a compound produced by the fungus Fusicoccum amygdali Del. In plant cells, FC complexes with 14-3-3 proteins to activate H+ pumping across the plasma membrane. It has long been thought that FC acts on higher plants only; here, we show that exposing frog embryos to FC during early development specifically results in randomization of the asymmetry of the left-right (LR) axis (heterotaxia). Biochemical and molecular-genetic evidence is presented that 14-3-3-family proteins are an obligate component of Xenopus FC receptors and that perturbation of 14-3-3 protein function results in heterotaxia. The subcellular localization of 14-3-3 mRNAs and proteins reveals novel cytoplasmic destinations, and a left-right asymmetry at the first cell division. Using gain-of-function and loss-of-function experiments, we show that 14-3-3E protein is likely to be an endogenous and extremely early aspect of LR patterning. These data highlight a striking conservation of signaling pathways across kingdoms, suggest common mechanisms of polarity establishment between C. elegans and vertebrate embryos, and uncover a novel entry point into the pathway of left-right asymmetry determination.

Key words: Left-right asymmetry, 14-3-3 protein, Fusicoccin, Xenopus


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© The Company of Biologists Ltd 2003