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Whole-mount Immunohistochemical Analysis for Embryonic Limb Skin Vasculature: a Model System to Study Vascular Branching Morphogenesis in Embryo
Published on: May 20, 2011
Sphingosine 1-phosphate receptor signaling regulates proper embryonic vascular patterning
Karen Mendelson1, Tomasz Zygmunt, Jesús Torres-Vázquez
1Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, New York 10021, USA.
The Journal of Biological Chemistry
|December 12, 2012
Summary
Zebrafish possess conserved sphingosine 1-phosphate (S1P) receptors crucial for vascular development. Knockdown of S1P receptor 1 (s1pr1) and S1P receptor 2 (s1pr2) reveals their cooperative role in regulating blood vessel formation.
Area of Science:
- Vascular Biology
- Developmental Biology
- Zebrafish Models
Background:
- Sphingosine 1-phosphate (S1P) signaling through G-protein-coupled receptors regulates vital physiological processes, particularly in the vascular and immune systems.
- While S1P receptors are well-studied in mammals, their conservation and function in other vertebrates, like zebrafish, remain less explored.
Purpose of the Study:
- To investigate the conservation and function of S1P receptors and related enzymes in the zebrafish genome.
- To elucidate the role of specific S1P receptors (s1pr1 and s1pr2) in zebrafish vascular development and angiogenesis.
Main Methods:
- Bioinformatic analysis to identify S1P receptor-like sequences in the zebrafish genome.
- Sphingolipidomic analysis to quantify S1P and related metabolites in zebrafish.
- Morpholino-mediated knockdown of s1pr1 and s1pr2 to assess vascular phenotypes.
- Co-expression analysis of s1pr1, s1pr2, and the S1P transporter spns2.
Main Results:
- Seven S1P receptor-like sequences, including duplicated orthologs, were identified in zebrafish.
- Knockdown of s1pr1 resulted in edema, circulatory defects, and altered vascularization.
- Co-suppression of s1pr1 and s1pr2, or s1pr1 and spns2, revealed cooperative functions essential for normal intersegmental vessel development.
Conclusions:
- Zebrafish possess a conserved S1P receptor system regulating vascular development.
- S1P receptors s1pr1 and s1pr2, along with the transporter spns2, function cooperatively to control angiogenesis in zebrafish.
- Extracellular S1P signaling via vascular S1P receptors is critical for embryonic vascular development.
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