The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis.
Sphingosine-1-phosphate (S1P) elicits diverse cellular responses through a family of G-protein-coupled receptors. We have shown previously that genetic disruption of the S1P(1) receptor, the most widely expressed of the family, results in embryonic lethality because of its key role within endothelial cells in regulating the coverage of blood vessels by vascular smooth muscle cells. To understand the physiologic functions of the two other widely expressed S1P receptors, we generated S1P(2) and S1P(3) null mice. Neither the S1P(2) null mice nor the S1P(3) null mice exhibited significant embryonic lethality or obvious phenotypic abnormalities. To unmask possible overlapping or collaborative functions between the S1P(1), S1P(2), and S1P(3) receptors, we examined embryos with multiple S1P receptor mutations. We found that S1P(1) S1P(2) double null and S1P(1) S1P(2) S1P(3) triple null embryos displayed a substantially more severe vascular phenotype than did embryos with only S1P(1) deleted. We also found partial embryonic lethality and vascular abnormalities in S1P(2) S1P(3) double null embryos. Our results indicate that the S1P(1), S1P(2) and S1P(3) receptors have redundant or cooperative functions for the development of a stable and mature vascular system during embryonic development.
Kono
Mari
M
Genetics of Development and Disease Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mi
Yide
Y
Liu
Yujing
Y
Sasaki
Teiji
T
Allende
Maria Laura
ML
Wu
Yun-Ping
YP
Yamashita
Tadashi
T
Proia
Richard L
RL
D000818:Animals; D001808:Blood Vessels / Q000033:anatomy & histology / Q000196:embryology* / Q000473:pathology; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D005865:Gestational Age; D006470:Hemorrhage; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D010641:Phenotype; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D049312:Receptors, Lysophospholipid
D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid