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Published on: October 19, 2013
A molecular pathway leading to endoderm formation in zebrafish
1Department of Biochemistry and Biophysics, Programs in Developmental Biology and Human Genetics, University of California at San Francisco, San Francisco, California 94143-0448, USA.
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.
Insights
Researchers identified a molecular pathway for zebrafish endoderm formation. Nodal-related molecules and One-eyed pinhead (Oep) activate Mixer, which acts through casanova to promote Sox17 expression and endoderm differentiation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Vertebrate endoderm development involves key regulators like growth factors, transcription factors (Mixer, Sox17, HNF3beta), and zebrafish One-eyed pinhead (Oep).
- The zebrafish casanova gene plays a crucial cell-autonomous role in endoderm formation.
Purpose of the Study:
- To elucidate the molecular pathway governing zebrafish endoderm formation.
- To investigate the roles of Sox17, casanova, Mixer, Oep, and TGF-beta signaling in this process.
Main Methods:
- Analysis of zebrafish mutants and overexpression studies.
- Examining gene expression patterns, including Sox17 and Mixer.
- Investigating the effects of manipulating signaling pathways like TGF-beta.
Main Results:
- Zebrafish Sox17 is expressed exclusively in the endoderm during gastrulation; casanova mutants lack Sox17 expression.
- Mixer overexpression induces ectopic Sox17 expression and promotes endoderm formation in oep mutants, but not in casanova mutants.
- Nodal-related molecules (Cyclops, Squint) and Oep are essential for normal Mixer expression; TGF-beta receptor activation promotes Sox17 expression.
Conclusions:
- A pathway exists where Cyclops and Squint activate receptors (e.g., TARAM-A), with Oep acting upstream.
- Signals activate Mixer, which then acts through casanova to induce Sox17 expression and endoderm differentiation.
