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Journal of Lipid Research, Vol. 44, 172-181, January 2003
Copyright © 2003 by Lipid Research, Inc.

Sterol effects and sites of sterol accumulation in Caenorhabditis elegans

: developmental requirement for 4-methyl sterols

Mark Merris^*, William G. Wadsworth, Uttam Khamrai, Robert Bittman, David J. Chitwood^** and John Lenard^1,*

^* Departments of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854
Pathology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854
Department of Chemistry and Biochemistry, Queens College, City University of New York, Flushing, NY 11367-1597
^** US Department of Agriculture, Agricultural Research Service, Nematology Laboratory, Beltsville, MD 20705

¹ To whom correspondence should be addressed. e-mail: lenard{at}umdnj.edu

Caenorhabditis elegans requires sterol, usually supplied as cholesterol, but this is enzymatically modified, and different sterols can substitute. Sterol deprivation decreased brood size and adult growth in the first generation, and completely, reversibly, arrested growth as larvae in the second. After one generation of sterol deprivation, 10 ng/ml cholesterol allowed delayed laying of a few eggs, but full growth required 300 ng/ml. C. elegans synthesizes two unusual 4-methyl sterols (4MSs), but each 4MS supported only limited growth as the sole sterol. However, addition of only 10 ng of cholesterol to 1,000 ng of 4MS restored full growth and egg-laying, suggesting that both a 4MS and an unmethylated sterol are required for development. Filipin stained sterols in only a few specific cells: the excretory gland cell, two amphid socket cells, two phasmid socket cells and, in males, spicule socket cells. Sterols were also present in the pharynx and in the intestine of feeding animals in a proximal-to-distal gradient.

This non-random sterol distribution, the low concentration requirements, and the effects of 4MSs argues that sterols are unlikely to be used for bulk structural modification of cell membranes, but may be required as hormone precursors and/or developmental effectors.

Supplementary key words cholesterol • filipin • amphid socket cell • phasmid socket cell • excretory gland cell

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