The activity of the Nodal antagonist Cerl-2 in the mouse node is required for correct L/R body axis

  1. Sara Marques1,
  2. Ana Cristina Borges1,2,
  3. Ana Cristina Silva1,2,
  4. Sandra Freitas1,
  5. Michelangelo Cordenonsi3, and
  6. José António Belo1,2,4
  1. 1Instituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal; 2Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, Campus de Gambelas, 8000-010 Faro, Portugal; 3Department of Histology, Microbiology, and Medical Biotechnologies, Section of Histology and Embryology, University of Padua, 35121 Padua, Italy

Abstract

Correct establishment of the left/right (L/R) body asymmetry in the mouse embryo requires asymmetric activation of the evolutionarily conserved Nodal signaling cascade in the left lateral plate mesoderm (L-LPM). Furthermore, the presence of Nodal in the node is essential for its own expression in the L-LPM. Here, we have characterized the function of cerl-2, a novel Nodal antagonist, which displays a unique asymmetric expression on the right side of the mouse node. cerl-2 knockout mice display multiple laterality defects including randomization of the L/R axis. These defects can be partially rescued by removing one nodal allele. Our results demonstrate that Cerl-2 plays a key role in restricting the Nodal signaling pathway toward the left side of the mouse embryo by preventing its activity in the right side.

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Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.306504.

  • 4 Corresponding author. E-MAIL jbelo{at}igc.gulbenkian.pt; FAX 351-21-4407970.

    • Accepted August 4, 2004.
    • Received April 22, 2004.
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