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

Angel Raya, Yasuhiko Kawakami, Concepción Rodríguez-Esteban, Dirk Büscher, Christopher M. Koth, Tohru Itoh, Masanobu Morita, R. Marina Raya, Ilir Dubova, Joaquín Grego Bessa, José Luis De la Pompa, Juan Carlos Izpisúa Belmonte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

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 for Nodal expression around the node, and for proper left-right determination. We identify Notch-responsive elements in the Nodal 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.

Original languageEnglish (US)
Pages (from-to)1213-1218
Number of pages6
JournalGenes and Development
Volume17
Issue number10
DOIs
StatePublished - May 15 2003
Externally publishedYes

Keywords

  • Left-right asymmetry
  • Nodal
  • Notch signaling
  • Pitx2
  • Sonic hedgehog
  • Zebrafish

ASJC Scopus subject areas

  • General Medicine

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