This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mizugishi, K.
Right arrow Articles by Proia, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mizugishi, K.
Right arrow Articles by Proia, R. L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2005, p. 11113-11121, Vol. 25, No. 24
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.24.11113-11121.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Essential Role for Sphingosine Kinases in Neural and Vascular Development

Kiyomi Mizugishi,1 Tadashi Yamashita,1 Ana Olivera,2 Georgina F. Miller,3 Sarah Spiegel,4 and Richard L. Proia1*

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 232984

Received 8 August 2005/ Returned for modification 10 September 2005/ Accepted 1 October 2005

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. S1P1 receptor-null mice also showed severe defects in neurogenesis, indicating that the mechanism by which S1P promotes neurogenesis is, in part, signaling from the S1P1 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.

* Corresponding author. Mailing address: Genetics of Development and Disease Branch, NIDDK, National Institutes of Health, Bldg. 10, Rm. 9N-314, 10 Center Dr., MSC 1821, Bethesda, MD 20892-1821. Phone: (301) 496-4391. Fax: (301) 496-0839. E-mail: proia{at}nih.gov.

Molecular and Cellular Biology, December 2005, p. 11113-11121, Vol. 25, No. 24
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.24.11113-11121.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Takuwa, N., Ohkura, S.-I., Takashima, S.-I., Ohtani, K., Okamoto, Y., Tanaka, T., Hirano, K., Usui, S., Wang, F., Du, W., Yoshioka, K., Banno, Y., Sasaki, M., Ichi, I., Okamura, M., Sugimoto, N., Mizugishi, K., Nakanuma, Y., Ishii, I., Takamura, M., Kaneko, S., Kojo, S., Satouchi, K., Mitumori, K., Chun, J., Takuwa, Y. (2009). S1P3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species. Cardiovasc Res 0: cvp312v2-cvp312 [Abstract] [Full Text]  
  • Daum, G., Grabski, A., Reidy, M.A. (2009). Sphingosine 1-Phosphate: A Regulator of Arterial Lesions. Arterioscler. Thromb. Vasc. Bio. 29: 1439-1443 [Abstract] [Full Text]  
  • Miranda, G. E., Abrahan, C. E., Politi, L. E., Rotstein, N. P. (2009). Sphingosine-1-Phosphate Is a Key Regulator of Proliferation and Differentiation in Retina Photoreceptors. IOVS 50: 4416-4428 [Abstract] [Full Text]  
  • Lai, W.-Q., Irwan, A. W., Goh, H. H., Melendez, A. J., McInnes, I. B., Leung, B. P. (2009). Distinct Roles of Sphingosine Kinase 1 and 2 in Murine Collagen-Induced Arthritis. J. Immunol. 183: 2097-2103 [Abstract] [Full Text]  
  • Pushparaj, P. N., Manikandan, J., Tay, H. K., H'ng, S. C., Kumar, S. D., Pfeilschifter, J., Huwiler, A., Melendez, A. J. (2009). Sphingosine Kinase1 Is Pivotal for Fc{epsilon}RI-Mediated Mast Cell Signaling and Functional Responses In Vitro and In Vivo. J. Immunol. 183: 221-227 [Abstract] [Full Text]  
  • Hayashi, H., Nakagami, H., Takami, Y., Koriyama, H., Mori, M., Tamai, K., Sun, J., Nagao, K., Morishita, R., Kaneda, Y. (2009). FHL-2 Suppresses VEGF-Induced Phosphatidylinositol 3-Kinase/Akt Activation via Interaction With Sphingosine Kinase-1. Arterioscler. Thromb. Vasc. Bio. 29: 909-914 [Abstract] [Full Text]  
  • Gaengel, K., Genove, G., Armulik, A., Betsholtz, C. (2009). Endothelial-Mural Cell Signaling in Vascular Development and Angiogenesis. Arterioscler. Thromb. Vasc. Bio. 29: 630-638 [Abstract] [Full Text]  
  • Karliner, J. S. (2009). Sphingosine kinase regulation and cardioprotection. Cardiovasc Res 82: 184-192 [Abstract] [Full Text]  
  • Igarashi, J., Michel, T. (2009). Sphingosine-1-phosphate and modulation of vascular tone. Cardiovasc Res 82: 212-220 [Abstract] [Full Text]  
  • Wadgaonkar, R., Patel, V., Grinkina, N., Romano, C., Liu, J., Zhao, Y., Sammani, S., Garcia, J. G. N., Natarajan, V. (2009). Differential regulation of sphingosine kinases 1 and 2 in lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol. 296: L603-L613 [Abstract] [Full Text]  
  • Maceyka, M., Milstien, S., Spiegel, S. (2009). Sphingosine-1-phosphate: the Swiss army knife of sphingolipid signaling. J. Lipid Res. 50: S272-S276 [Abstract] [Full Text]  
  • Skoura, A., Hla, T. (2009). Lysophospholipid receptors in vertebrate development, physiology, and pathology. J. Lipid Res. 50: S293-S298 [Abstract] [Full Text]  
  • Niessen, F., Furlan-Freguia, C., Fernandez, J. A., Mosnier, L. O., Castellino, F. J., Weiler, H., Rosen, H., Griffin, J. H., Ruf, W. (2009). Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality. Blood 113: 2859-2866 [Abstract] [Full Text]  
  • Kirby, R. J., Jin, Y., Fu, J., Cubillos, J., Swertfeger, D., Arend, L. J. (2009). Dynamic regulation of sphingosine-1-phosphate homeostasis during development of mouse metanephric kidney. Am. J. Physiol. Renal Physiol. 296: F634-F641 [Abstract] [Full Text]  
  • Pederson, L., Ruan, M., Westendorf, J. J., Khosla, S., Oursler, M. J. (2008). Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc. Natl. Acad. Sci. USA 105: 20764-20769 [Abstract] [Full Text]  
  • Uhlig, S., Gulbins, E. (2008). Sphingolipids in the Lungs. Am. J. Respir. Crit. Care Med. 178: 1100-1114 [Abstract] [Full Text]  
  • Ye, X. (2008). Lysophospholipid signaling in the function and pathology of the reproductive system. Hum Reprod Update 14: 519-536 [Abstract] [Full Text]  
  • Wu, Y.-P., Mizugishi, K., Bektas, M., Sandhoff, R., Proia, R. L. (2008). Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease. Hum Mol Genet 17: 2257-2264 [Abstract] [Full Text]  
  • Takabe, K., Paugh, S. W., Milstien, S., Spiegel, S. (2008). "Inside-Out" Signaling of Sphingosine-1-Phosphate: Therapeutic Targets. Pharmacol. Rev. 60: 181-195 [Abstract] [Full Text]  
  • Oyama, O., Sugimoto, N., Qi, X., Takuwa, N., Mizugishi, K., Koizumi, J., Takuwa, Y. (2008). The lysophospholipid mediator sphingosine-1-phosphate promotes angiogenesis in vivo in ischaemic hindlimbs of mice. Cardiovasc Res 78: 301-307 [Abstract] [Full Text]  
  • Igarashi, J., Michel, T. (2008). The Enigma of Sphingosine 1-Phosphate Synthesis: A Novel Role for Endothelial Sphingosine Kinases. Circ. Res. 102: 630-632 [Full Text]  
  • Venkataraman, K., Lee, Y.-M., Michaud, J., Thangada, S., Ai, Y., Bonkovsky, H. L., Parikh, N. S., Habrukowich, C., Hla, T. (2008). Vascular Endothelium As a Contributor of Plasma Sphingosine 1-Phosphate. Circ. Res. 102: 669-676 [Abstract] [Full Text]  
  • Sankala, H. M., Hait, N. C., Paugh, S. W., Shida, D., Lepine, S., Elmore, L. W., Dent, P., Milstien, S., Spiegel, S. (2007). Involvement of Sphingosine Kinase 2 in p53-Independent Induction of p21 by the Chemotherapeutic Drug Doxorubicin. Cancer Res. 67: 10466-10474 [Abstract] [Full Text]  
  • Zwerts, F., Lupu, F., De Vriese, A., Pollefeyt, S., Moons, L., Altura, R. A., Jiang, Y., Maxwell, P. H., Hill, P., Oh, H., Rieker, C., Collen, D., Conway, S. J., Conway, E. M. (2007). Lack of endothelial cell survivin causes embryonic defects in angiogenesis, cardiogenesis, and neural tube closure. Blood 109: 4742-4752 [Abstract] [Full Text]  
  • Don, A. S., Martinez-Lamenca, C., Webb, W. R., Proia, R. L., Roberts, E., Rosen, H. (2007). Essential Requirement for Sphingosine Kinase 2 in a Sphingolipid Apoptosis Pathway Activated by FTY720 Analogues. J. Biol. Chem. 282: 15833-15842 [Abstract] [Full Text]  
  • Kajimoto, T., Okada, T., Yu, H., Goparaju, S. K., Jahangeer, S., Nakamura, S.-i. (2007). Involvement of Sphingosine-1-Phosphate in Glutamate Secretion in Hippocampal Neurons. Mol. Cell. Biol. 27: 3429-3440 [Abstract] [Full Text]  
  • Hait, N. C., Bellamy, A., Milstien, S., Kordula, T., Spiegel, S. (2007). Sphingosine Kinase Type 2 Activation by ERK-mediated Phosphorylation. J. Biol. Chem. 282: 12058-12065 [Abstract] [Full Text]  
  • Pappu, R., Schwab, S. R., Cornelissen, I., Pereira, J. P., Regard, J. B., Xu, Y., Camerer, E., Zheng, Y.-W., Huang, Y., Cyster, J. G., Coughlin, S. R. (2007). Promotion of Lymphocyte Egress into Blood and Lymph by Distinct Sources of Sphingosine-1-Phosphate. Science 316: 295-298 [Abstract] [Full Text]  
  • Krishnamurthy, K., Wang, G., Silva, J., Condie, B. G., Bieberich, E. (2007). Ceramide Regulates Atypical PKC{zeta}/{lambda}-mediated Cell Polarity in Primitive Ectoderm Cells: A NOVEL FUNCTION OF SPHINGOLIPIDS IN MORPHOGENESIS. J. Biol. Chem. 282: 3379-3390 [Abstract] [Full Text]  
  • Spiegel, S., Milstien, S. (2007). Functions of the Multifaceted Family of Sphingosine Kinases and Some Close Relatives. J. Biol. Chem. 282: 2125-2129 [Full Text]  
  • Aplin, A. C., Gelati, M., Fogel, E., Carnevale, E., Nicosia, R. F. (2006). Angiopoietin-1 and vascular endothelial growth factor induce expression of inflammatory cytokines before angiogenesis. Physiol. Genomics 27: 20-28 [Abstract] [Full Text]  
  • Kohno, M., Momoi, M., Oo, M. L., Paik, J.-H., Lee, Y.-M., Venkataraman, K., Ai, Y., Ristimaki, A. P., Fyrst, H., Sano, H., Rosenberg, D., Saba, J. D., Proia, R. L., Hla, T. (2006). Intracellular role for sphingosine kinase 1 in intestinal adenoma cell proliferation.. Mol. Cell. Biol. 26: 7211-7223 [Abstract] [Full Text]  
  • Xu, R., Jin, J., Hu, W., Sun, W., Bielawski, J., Szulc, Z., Taha, T., Obeid, L. M., Mao, C. (2006). Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P. FASEB J. 20: 1813-1825 [Abstract] [Full Text]  
  • Tanaka, M., Okudaira, S., Kishi, Y., Ohkawa, R., Iseki, S., Ota, M., Noji, S., Yatomi, Y., Aoki, J., Arai, H. (2006). Autotaxin Stabilizes Blood Vessels and Is Required for Embryonic Vasculature by Producing Lysophosphatidic Acid. J. Biol. Chem. 281: 25822-25830 [Abstract] [Full Text]  
  • van Meeteren, L. A., Ruurs, P., Stortelers, C., Bouwman, P., van Rooijen, M. A., Pradere, J. P., Pettit, T. R., Wakelam, M. J. O., Saulnier-Blache, J. S., Mummery, C. L., Moolenaar, W. H., Jonkers, J. (2006). Autotaxin, a Secreted Lysophospholipase D, Is Essential for Blood Vessel Formation during Development.. Mol. Cell. Biol. 26: 5015-5022 [Abstract] [Full Text]  
  • Guthridge, M. A., Goodall, G. J., Pitson, S. M. (2006). Meeting Report: Barossa 2005--Signaling Networks. Sci Signal 2006: pe9-pe9 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»