Essential Role for Sphingosine Kinases in Neural and Vascular Development
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| Published in | Molecular and Cellular Biology Vol. 25; no. 24; pp. 11113 - 11121 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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United States
American Society for Microbiology
01.12.2005
Taylor & Francis |
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| Online Access | Get full text |
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| AbstractList | 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. 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. 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 sub(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 sub(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. Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology. For an alternate route to MCB .asm.org, visit: MCB |
| Author | Georgina F. Miller Kiyomi Mizugishi Ana Olivera Sarah Spiegel Richard L. Proia Tadashi Yamashita |
| AuthorAffiliation | Genetics of Development and Disease Branch, NIDDK, 1 Molecular Immunology and Inflammation Branch, NIAMS, 2 Division of Veterinary Resources, National Institutes of Health, Bethesda, Maryland 20892, 3 Department of Biochemistry, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298 4 |
| AuthorAffiliation_xml | – name: Genetics of Development and Disease Branch, NIDDK, 1 Molecular Immunology and Inflammation Branch, NIAMS, 2 Division of Veterinary Resources, National Institutes of Health, Bethesda, Maryland 20892, 3 Department of Biochemistry, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298 4 |
| Author_xml | – sequence: 1 givenname: Kiyomi surname: Mizugishi fullname: Mizugishi, Kiyomi organization: Genetics of Development and Disease Branch, NIDDK – sequence: 2 givenname: Tadashi surname: Yamashita fullname: Yamashita, Tadashi organization: Genetics of Development and Disease Branch, NIDDK – sequence: 3 givenname: Ana surname: Olivera fullname: Olivera, Ana organization: Molecular Immunology and Inflammation Branch, NIAMS – sequence: 4 givenname: Georgina F. surname: Miller fullname: Miller, Georgina F. organization: Division of Veterinary Resources, National Institutes of Health – sequence: 5 givenname: Sarah surname: Spiegel fullname: Spiegel, Sarah organization: Department of Biochemistry, Virginia Commonwealth University School of Medicine – sequence: 6 givenname: Richard L. surname: Proia fullname: Proia, Richard L. email: proia@nih.gov organization: Genetics of Development and Disease Branch, NIDDK |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16314531$$D View this record in MEDLINE/PubMed |
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Mendeley... Sphingosine-1-phosphate (S1P), an important sphingolipid metabolite, regulates diverse cellular processes, including cell survival, growth, and... |
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| SubjectTerms | Animals Apoptosis - genetics Blood Vessels - abnormalities Blood Vessels - embryology Blood Vessels - enzymology Lysophospholipids - metabolism Mice Mice, Knockout Mitosis - genetics Neovascularization, Physiologic - genetics Nervous System - embryology Nervous System - enzymology Neural Tube Defects - enzymology Neural Tube Defects - genetics Phosphotransferases (Alcohol Group Acceptor) - genetics Phosphotransferases (Alcohol Group Acceptor) - physiology Receptors, Lysosphingolipid - genetics Receptors, Lysosphingolipid - metabolism Signal Transduction Sphingosine - analogs & derivatives Sphingosine - metabolism |
| Title | Essential Role for Sphingosine Kinases in Neural and Vascular Development |
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