casanova encodes a novel Sox-related protein necessary and sufficient for early endoderm formation in zebrafish

Genes Dev. 2001 Jun 15;15(12):1493-505. doi: 10.1101/gad.892301.


Early endoderm formation in zebrafish requires at least three loci that function downstream of Nodal signaling but upstream of the early endodermal marker sox17: bonnie and clyde (bon), faust (fau), and casanova (cas). cas mutants show the most severe phenotype as they do not form any gut tissue and lack all sox17 expression. Activation of the Nodal signaling pathway or overexpression of Bon or Fau/Gata5 fails to restore any sox17 expression in cas mutants, demonstrating that cas plays a central role in endoderm formation. Here we show that cas encodes a novel member of the Sox family of transcription factors. Initial cas expression appears in the dorsal yolk syncytial layer (YSL) in the early blastula, and is independent of Nodal signaling. In contrast, endodermal expression of cas, which begins in the late blastula, is regulated by Nodal signaling. Cas is a potent inducer of sox17 expression in wild-type embryos as well as in bon and fau/gata5 mutants. Cas is also a potent inducer of sox17 expression in MZoep mutants, which cannot respond to Nodal signaling. In addition, ectopic expression of cas in presumptive mesodermal cells leads to their transfating into endoderm. Altogether, these data indicate that Cas is the principal transcriptional effector of Nodal signaling during zebrafish endoderm formation.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation
  • DNA-Binding Proteins / metabolism
  • Endoderm / physiology*
  • GATA5 Transcription Factor
  • Gene Expression Regulation, Developmental
  • High Mobility Group Proteins / classification
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Homeodomain Proteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mesoderm / cytology
  • Mesoderm / physiology
  • Molecular Sequence Data
  • Nodal Signaling Ligands
  • Proteins / genetics
  • SOX Transcription Factors
  • SOXF Transcription Factors
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*
  • Transcription Factors / classification
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta / genetics
  • Zebrafish
  • Zebrafish Proteins*


  • DNA-Binding Proteins
  • GATA5 Transcription Factor
  • GATA5 protein, human
  • High Mobility Group Proteins
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nodal Signaling Ligands
  • Proteins
  • SOX Transcription Factors
  • SOX17 protein, human
  • SOXF Transcription Factors
  • Transcription Factors
  • Transforming Growth Factor beta
  • Zebrafish Proteins
  • gata5 protein, zebrafish
  • ndr1 protein, zebrafish
  • ndr2 protein, zebrafish
  • sox17 protein, zebrafish
  • sox32 protein, zebrafish