Reciprocal signaling between the ectoderm and a mesendodermal left-right organizer directs left-right determination in the sea urchin embryo

PLoS Genet. 2012;8(12):e1003121. doi: 10.1371/journal.pgen.1003121. Epub 2012 Dec 13.

Abstract

During echinoderm development, expression of nodal on the right side plays a crucial role in positioning of the rudiment on the left side, but the mechanisms that restrict nodal expression to the right side are not known. Here we show that establishment of left-right asymmetry in the sea urchin embryo relies on reciprocal signaling between the ectoderm and a left-right organizer located in the endomesoderm. FGF/ERK and BMP2/4 signaling are required to initiate nodal expression in this organizer, while Delta/Notch signaling is required to suppress formation of this organizer on the left side of the archenteron. Furthermore, we report that the H(+)/K(+)-ATPase is critically required in the Notch signaling pathway upstream of the S3 cleavage of Notch. Our results identify several novel players and key early steps responsible for initiation, restriction, and propagation of left-right asymmetry during embryogenesis of a non-chordate deuterostome and uncover a functional link between the H(+)/K(+)-ATPase and the Notch signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism
  • Ectoderm / growth & development*
  • Embryo, Nonmammalian
  • Embryonic Development / genetics
  • Gene Expression Regulation, Developmental
  • H(+)-K(+)-Exchanging ATPase* / genetics
  • H(+)-K(+)-Exchanging ATPase* / metabolism
  • Left-Right Determination Factors / genetics*
  • MAP Kinase Signaling System
  • Receptors, Notch* / genetics
  • Receptors, Notch* / metabolism
  • Sea Urchins* / embryology
  • Sea Urchins* / growth & development
  • Signal Transduction

Substances

  • Bone Morphogenetic Protein 2
  • Left-Right Determination Factors
  • Receptors, Notch
  • H(+)-K(+)-Exchanging ATPase

Grants and funding

This work was supported by grants from the Association pour la Recherche contre le Cancer (ARC 3801 and 4908), the Agence Nationale pour la Recherche (ANR), the CNRS, the University Pierre et Marie Curie Paris, and the Fondation Bettencourt Schueller. NB was recipient of a fellowship from the Fondation pour la Recherche Medicale (FRM) (prize Line Pomaret-Delalande). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.