The ceramide synthase 2b gene mediates genomic sensing and regulation of sphingosine Levels during zebrafish embryogenesis
- Cornell University, United States
- Boston Children's Hospital, United States
- Icahn School of Medicine at Mount Sinai, United States
- Harvard Medical School, United States
Abstract
Sphingosine-1-phosphate (S1P) is generated through phosphorylation of sphingosine by sphingosine kinases (Sphk1 and Sphk2). We show that sphk2 maternal-zygotic mutant zebrafish embryos (sphk2MZ) display early developmental phenotypes, including a delay in epiboly, depleted S1P levels, elevated levels of sphingosine, and resistance to sphingosine toxicity. The sphk2MZ embryos also have strikingly increased levels of maternal transcripts encoding ceramide synthase 2b (Cers2b), and loss of Cers2b in sphk2MZ embryos phenocopies sphingosine toxicity. An upstream region of the cers2b promoter supports enhanced expression of a reporter gene in sphk2MZ embryos compared to wildtype embryos. Furthermore, ectopic expression of Cers2b protein itself reduces activity of the promoter, and this repression is relieved by exogenous sphingosine. Therefore, the sphk2MZ genome recognizes the lack of sphingosine kinase activity and up-regulates cers2b as a salvage pathway for sphingosine turnover. Cers2b can also function as a sphingolipid-responsive factor to mediate at least part of a feedback regulatory mechanism.
Article and author information
Author details
Funding
National Institutes of Health (HL089934)
- Timothy Hla
National Institutes of Health (CA077839)
- Timothy Hla
National Institutes of Health (HL111400)
- Todd Evans
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (2011-100) of the Weill Cornell Medical College.
Copyright
© 2017, Mendelson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The ceramide synthase 2b gene mediates genomic sensing and regulation of sphingosine Levels during zebrafish embryogenesis
eLife 6:e21992.
https://doi.org/10.7554/eLife.21992
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