ZFIN ID: ZDB-PUB-991102-6
A molecular pathway leading to endoderm formation in zebrafish
Alexander, J. and Stainier, D.Y.
Date: 1999
Source: Current biology : CB 9(20): 1147-1157 (Journal)
Registered Authors: Alexander, Jon, Stainier, Didier
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • DNA-Binding Proteins*
  • Endoderm/cytology
  • Endoderm/metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • High Mobility Group Proteins*
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Molecular Sequence Data
  • Mutation
  • Nodal Signaling Ligands
  • Protein-Serine-Threonine Kinases*
  • Proteins/genetics
  • Receptors, Growth Factor/genetics
  • Receptors, Transforming Growth Factor beta*
  • SOXF Transcription Factors
  • Signal Transduction
  • Transcription Factors*
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins*
PubMed: 10531029 Full text @ Curr. Biol.
ABSTRACT
Background: Several potentially important regulators of vertebrate endoderm development have been identified, including Activin-related growth factors and their receptors; transcriptional regulators encoded by the genes Mixer, Xsox17, and HNF3beta; zebrafish One-eyed pinhead (Oep), a member of the Cripto/FRL-1/Cryptic family of epidermal growth factor related proteins (EGF-CFC); and the product of the zebrafish locus casanova, which plays an essential cell-autonomous role in endoderm formation. Results: Using overexpression studies and the analysis of different zebrafish mutants, we have assembled a molecular pathway that leads to endoderm formation. We report that a zebrafish Sox17 homologue is expressed during gastrulation exclusively in the endoderm and that casanova mutants lack all sox17 expression. Overexpression of mixer induces ectopic sox17-expressing cells in wild-type embryos and promotes endoderm formation in oep mutants, but does not rescue sox17 expression or endoderm formation in casanova mutants. Overexpression of a constitutively active form of the type I transforming growth factor beta (TGF-beta) receptor TARAM-A also promotes sox17 expression in wild-type and oep mutant embryos, but not in casanova mutants. We also show that the Nodal-related molecules Cyclops and Squint and the transmembrane protein Oep are essential for normal mixer expression. Conclusions: The data indicate that the following pathway leads to zebrafish endoderm formation: Cyclops and Squint activate receptors such as TARAM-A; Oep also appears to act upstream of such receptors; signals transduced by these receptors lead to the expression of mixer, Mixer then acts through casanova to promote the expression of sox17 and differentiation of the endoderm.
ADDITIONAL INFORMATIONNo data available