The novel Cer-like protein Caronte mediates the establishment of embryonic left-right asymmetry.
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.
Rodríguez Esteban
C
C
The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA.
Capdevila
J
J
Economides
A N
AN
Pascual
J
J
Ortiz
A
A
Izpisúa Belmonte
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D019556:COS Cells; D002642:Chick Embryo; D003001:Cloning, Molecular; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D055458:Left-Right Determination Factors; D008969:Molecular Sequence Data; D055457:Nodal Protein; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D029867:Xenopus Proteins
D030161:Avian Proteins; D019485:Bone Morphogenetic Proteins; C496456:FGF8 protein, human; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C526161:LEFTY1 protein, human; D055458:Left-Right Determination Factors; C491536:NKX3-2 protein, human; C526007:NODAL protein, human; D055457:Nodal Protein; D011506:Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C121419:caronte protein, Gallus gallus; C100866:cer1 protein, Xenopus; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors