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Publication : Essential role for sphingosine kinases in neural and vascular development.

First Author  Mizugishi K Year  2005
Journal  Mol Cell Biol Volume  25
Issue  24 Pages  11113-21
PubMed ID  16314531 Mgi Jnum  J:103755
Mgi Id  MGI:3610689 Doi  10.1128/MCB.25.24.11113-11121.2005
Citation  Mizugishi K, et al. (2005) Essential role for sphingosine kinases in neural and vascular development. Mol Cell Biol 25(24):11113-21
abstractText  Sphingosine-1-phosphate (S1P), an important sphingolipid metabolite, regulates diverse cellular processes, including cell survival, growth, and differentiation. Here we show that S1P signaling is critical for neural and vascular development. Sphingosine kinase-null mice exhibited a deficiency of S1P which severely disturbed neurogenesis, including neural tube closure, and angiogenesis and caused embryonic lethality. A dramatic increase in apoptosis and a decrease in mitosis were seen in the developing nervous system. S1P(1) receptor-null mice also showed severe defects in neurogenesis, indicating that the mechanism by which S1P promotes neurogenesis is, in part, signaling from the S1P(1) receptor. Thus, S1P joins a growing list of signaling molecules, such as vascular endothelial growth factor, which regulate the functionally intertwined pathways of angiogenesis and neurogenesis. Our findings also suggest that exploitation of this potent neuronal survival pathway could lead to the development of novel therapeutic approaches for neurological diseases.
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