Notch activity induces Nodal expression and mediates the establishment of left–right asymmetry in vertebrate embryos

  1. Ángel Raya1,3,
  2. Yasuhiko Kawakami1,3,
  3. Concepción Rodrı́guez-Esteban1,3,
  4. Dirk Büscher1,
  5. Christopher M. Koth1,
  6. Tohru Itoh1,
  7. Masanobu Morita1,
  8. R. Marina Raya1,
  9. Ilir Dubova1,
  10. Joaquı́n Grego Bessa2,
  11. José Luis de la Pompa2, and
  12. Juan Carlos Izpisúa Belmonte1,4
  1. 1Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA; 2Molecular Oncology, Institut de Recerca Oncologica, Hospital Duran i Reynals, 08907 L'Hospitalet de Llobregat, Barcelona, Spain

Abstract

Left-sided expression of Nodal in the lateral plate mesoderm is a conserved feature necessary for the establishment of normal left–right asymmetry during vertebrate embryogenesis. By using gain- and loss-of-function experiments in zebrafish and mouse, we show that the activity of the Notch pathway is necessary and sufficient forNodal expression around the node, and for proper left–right determination. We identify Notch-responsive elements in theNodal promoter, and unveil a direct relationship between Notch activity and Nodal expression around the node. Our findings provide evidence for a mechanism involving Notch activity that translates an initial symmetry-breaking event into asymmetric gene expression.

Keywords

Footnotes

  • 3 These authors contributed equally to this work.

  • 4 Corresponding author.

  • E-MAIL belmonte{at}salk.edu; FAX (858) 453-2573.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1084403.

    • Received February 13, 2003.
    • Accepted March 28, 2003.
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