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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.
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.