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Vegfc is required for vascular development and endoderm morphogenesis in zebrafish
Elke A Ober1, Birgitta Olofsson, Taija Mäkinen
1Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, University of California, San Francisco, California 94143-0448, USA.
EMBO Reports
|January 8, 2004
Summary
Vascular endothelial growth factor C (Vegfc) unexpectedly regulates zebrafish endoderm development. This factor is crucial for dorsal endoderm formation and anterior endoderm coalescence, impacting gut tube and organ development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Endodermal morphogenesis is critical for forming the primitive gut tube and associated organs during embryogenesis.
- While endoderm differentiation genes are known, regulators of endodermal morphogenesis remain largely uncharacterized.
- Vascular endothelial growth factor C (Vegfc) is primarily recognized for its roles in angiogenesis and lymphangiogenesis.
Purpose of the Study:
- To investigate the role of vascular endothelial growth factor C (Vegfc) in endodermal morphogenesis during zebrafish embryogenesis.
- To elucidate the specific stages and mechanisms by which Vegfc influences endoderm development.
Main Methods:
- Utilized morpholino antisense oligonucleotides to reduce Vegfc levels in zebrafish embryos.
- Employed overexpression of a soluble form of the VEGFC receptor, VEGFR-3, to inhibit Vegfc signaling.
- Performed detailed analyses of endodermal cell behavior and organ formation in treated zebrafish embryos.
Main Results:
- Reduced Vegfc levels or inhibited Vegfc signaling resulted in abnormal anterior endoderm coalescence, leading to a forked gut tube.
- These manipulations also caused duplication of liver and pancreatic buds.
- Vegfc was found to be essential for the initial formation of the dorsal endoderm.
- Vegfc's role in vasculogenesis and angiogenesis in zebrafish embryos was also confirmed.
Conclusions:
- Vegfc signaling plays a surprisingly dual role in endoderm development, influencing both initial dorsal endoderm differentiation and anterior endoderm midline coalescence.
- These findings highlight a novel function for Vegfc beyond its established roles in vascular development, implicating it in fundamental aspects of gut tube formation.