A crucial component of the endoderm formation pathway, CASANOVA, is encoded by a novel sox-related gene

  1. Thomas Dickmeis1,4,
  2. Philippe Mourrain2,4,
  3. Laure Saint-Etienne2,
  4. Nadine Fischer1,
  5. Pia Aanstad3,
  6. Matthew Clark3,
  7. Uwe Strähle1, and
  8. Frédéric Rosa2,5
  1. 1Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, F-67404 Illkirch Cedex, C.U. de Strasbourg, France; 2U 368 INSERM, Ecole Normale Supérieure, F-75230 PARIS CEDEX 05, France; 3Max Planck Institut fuer Molekulare Genetik, D-14195 Berlin (Dahlem), Germany

Abstract

casanova (cas) mutant zebrafish embryos lack endoderm and develop cardia bifida. In a substractive screen for Nodal-responsive genes, we isolated an HMG box-containing gene,10J3, which is expressed in the endoderm. Thecas phenotype is rescued by overexpression of 10J3and can be mimicked by 10J3-directed morpholinos. Furthermore, we identified a mutation within 10J3 coding sequence that cosegregates with the cas phenotype, clearly demonstrating that cas is encoded by 10J3. Epistasis experiments are consistent with an instructive role forcas in endoderm formation downstream of Nodal signals and upstream of sox17. In the absence of casactivity, endoderm progenitors differentiate into mesodermal derivatives. Thus, cas is an HMG box-containing gene involved in the fate decision between endoderm and mesoderm that acts downstream of Nodal signals.

Keywords

Footnotes

  • 4 These two authors contributed equally to this work.

  • 5 Corresponding author.

  • E-MAIL rosa{at}wotan.ens.fr; FAX 33-01-44-32-39-88.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.196901.

    • Received December 22, 2000.
    • Accepted April 24, 2001.
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