1. Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA
2. Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
3. Department of Biology, University of San Diego, San Diego, California 92110, USA
4. Current address: Department of Anatomy and Neurobiology, College of Medicine, University of California, Irvine, California 92697-1280, USA.

Correspondence to: Gary Ruvkun¹ Correspondence and requests for materials should be addressed to G.R. (e-mail: Email: ruvkun@frodo.mgh.harvard.edu).

Abstract

The functions of serotonin have been assigned through serotonin-receptor-specific drugs and mutants^{1, 2}; however, because a constellation of receptors remains when a single receptor subtype is inhibited, the coordinate responses to modulation of serotonin levels may be missed. Here we report the analysis of behavioural and neuroendocrine defects caused by a complete lack of serotonin signalling. Analysis of the C. elegans genome sequence showed that there is a single tryptophan hydroxylase gene (tph-1)—the key enzyme for serotonin biosynthesis. Animals bearing a tph-1 deletion mutation do not synthesize serotonin but are fully viable. The tph-1 mutant shows abnormalities in behaviour and metabolism that are normally coupled with the sensation and ingestion of food: rates of feeding and egg laying are decreased; large amounts of fat are stored; reproductive lifespan is increased; and some animals arrest at the metabolically inactive dauer stage. This metabolic dysregulation is, in part, due to downregulation of tranforming growth factor- and insulin-like neuroendocrine signals. The action of the C. elegans serotonergic system in metabolic control is similar to mammalian serotonergic input to metabolism and obesity².