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doi: 10.1242/10.1242/dev.00456
1 Department of Biology and Molecular Biology Institute, San Diego State
University, San Diego, CA 92182-4614, USA
2 Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr
Way, Oakland, CA 94609, USA
* Authors for correspondence (e-mail: jsaba{at}chori.org and gharris{at}sunstroke.sdsu.edu)
Accepted 24 February 2003
Sphingosine-1-phosphate is a sphingolipid metabolite that regulates cell proliferation, migration and apoptosis through specific signaling pathways. Sphingosine-1-phosphate lyase catalyzes the conversion of sphingosine-1-phosphate to ethanolamine phosphate and a fatty aldehyde. We report the cloning of the Drosophila sphingosine-1-phosphate lyase gene (Sply) and demonstrate its importance for adult muscle development and integrity, reproduction and larval viability. Sply expression is temporally regulated, with onset of expression during mid-embryogenesis. Sply null mutants accumulate both phosphorylated and unphosphorylated sphingoid bases and exhibit semi-lethality, increased apoptosis in developing embryos, diminished egg-laying, and gross pattern abnormalities in dorsal longitudinal flight muscles. These defects are corrected by restoring Sply expression or by introduction of a suppressor mutation that diminishes sphingolipid synthesis and accumulation of sphingolipid intermediates. This is the first demonstration of novel and complex developmental pathologies directly linked to a disruption of sphingolipid catabolism in metazoans.
Key words: Sphingosine-1-phosphate, Sphingolipids, Sphingosine phosphate lyase, Muscle, Drosophila, Serine palmitoyltransferase, Sphingolipidoses, Reproduction, Apoptosis
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