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doi: 10.1242/10.1242/dev.00456

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Development 130, 2443-2453 (2003)
Copyright © 2003 The Company of Biologists Limited

Sply regulation of sphingolipid signaling molecules is essential for Drosophila development

Deron R. Herr1, Henrik Fyrst2, Van Phan1, Karie Heinecke2, Rana Georges1, Greg L. Harris1,* and Julie D. Saba2,*

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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© The Company of Biologists Ltd 2003