The novel Cer-like protein Caronte mediates the establishment of embryonic left-right asymmetry

Nature. 1999 Sep 16;401(6750):243-51. doi: 10.1038/45738.


In the chick embryo, left-right asymmetric patterns of gene expression in the lateral plate mesoderm are initiated by signals located in and around Hensen's node. Here we show that Caronte (Car), a secreted protein encoded by a member of the Cerberus/Dan gene family, mediates the Sonic hedgehog (Shh)-dependent induction of left-specific genes in the lateral plate mesoderm. Car is induced by Shh and repressed by fibroblast growth factor-8 (FGF-8). Car activates the expression of Nodal by antagonizing a repressive activity of bone morphogenic proteins (BMPs). Our results define a complex network of antagonistic molecular interactions between Activin, FGF-8, Lefty-1, Nodal, BMPs and Car that cooperate to control left-right asymmetry in the chick embryo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Avian Proteins*
  • Body Patterning / genetics
  • Body Patterning / physiology*
  • Bone Morphogenetic Proteins / physiology
  • COS Cells
  • Chick Embryo
  • Cloning, Molecular
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / physiology
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox
  • Hedgehog Proteins
  • Homeodomain Proteins / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Left-Right Determination Factors
  • Molecular Sequence Data
  • Nodal Protein
  • Proteins / genetics
  • Proteins / physiology*
  • Sequence Homology, Amino Acid
  • Trans-Activators*
  • Transcription Factors / physiology
  • Transforming Growth Factor beta / physiology
  • Xenopus Proteins


  • Avian Proteins
  • Bone Morphogenetic Proteins
  • FGF8 protein, human
  • Hedgehog Proteins
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • LEFTY1 protein, human
  • Left-Right Determination Factors
  • NKX3-2 protein, human
  • NODAL protein, human
  • Nodal Protein
  • Proteins
  • SHH protein, human
  • Trans-Activators
  • Transcription Factors
  • Transforming Growth Factor beta
  • Xenopus Proteins
  • caronte protein, Gallus gallus
  • cer1 protein, Xenopus
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors

Associated data

  • GENBANK/AF179483