Journal article
The Spinster Homolog, Two of Hearts, Is Required for Sphingosine 1-Phosphate Signaling in Zebrafish
N Osborne, K Brand-Arzamendi, EA Ober, SW Jin, H Verkade, NG Holtzman, D Yelon, DYR Stainier
Current Biology | CELL PRESS | Published : 2008
Abstract
The bioactive lipid sphingosine 1-phosphate (S1P) and its G protein-coupled receptors play critical roles in cardiovascular, immunological, and neural development and function [1-6]. Despite its importance, many questions remain about S1P signaling, including how S1P, which is synthesized intracellularly, is released from cells. Mutations in the zebrafish gene encoding the S1P receptor Miles Apart (Mil)/S1P2 disrupt the formation of the primitive heart tube [5]. We find that mutations of another zebrafish locus, two of hearts (toh), cause phenotypes that are morphologically indistinguishable from those seen in mil/s1p2 mutants. Positional cloning of toh reveals that it encodes a member of th..
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Awarded by National Science Foundation
Funding Acknowledgements
We thank Holly Field and Jonathan Alexander for assistance with initial studies of toh; Courtney Babbitt for assistance with phylogenetic analysis; Atsuo Kawahara for discussions and sharing of unpublished data; and Jason Cyster, Ian Scott, and Courtney Griffin for helpful comments on the manuscript. This work was supported in part by the National Science Foundation (N.O.), the American Heart Association (E.A.O., S-W.J., N.G.H.), the Human Frontier Science Program (H.V.), the National Institutes of Health (D.Y., D.Y.R.S.), and the Packard foundation (D.Y.R.S.).