239 Neuropeptide Gene Families in the Nematode Caenorhabditis elegans a CHRIS LI, b LAURA S. NELSON, b,c KYUHYUNG KIM, b ARIF NATHOO, d AND ANNE C. HART e,f b Department of Biology, Boston University, Boston, Massachusetts 02215, USA d Harvard University, Cambridge, Massachusetts 02138, USA e MGH Cancer Center and Department of Pathology, Harvard Medical School, Charlestown, Massachusetts 02129, USA ABSTRACT: Neuropeptides have diverse roles in the function and development of the nervous system. With the completion of the sequencing of the C. elegans genome, rapid identification of nematode neuropeptide genes is possible. To date, 41 C. elegans neuropeptide genes have been identified. Of these genes, 20 genes, named flp (F MRFamide-l ike p eptide) genes, encode FMRFamide-related proteins (FaRPs). Deletion of one of the flp genes, flp-1, results in several be- havioral defects, suggesting that at least one flp gene is not functionally redun- dant with other flp genes. Twenty-one genes, named n europeptide-l ike p rotein (nlp) genes, encode peptides distinct from the FaRP family. The predicted nlp- 1 and nlp-2 neuropeptides have modest similarity to buccalin and myomodulin, respectively. Cellular expression patterns and genetic analysis of flp and nlp genes suggest that neuropeptides in nematodes also have widespead and varied roles in nervous system function. INTRODUCTION Neuropeptides have been found throughout the animal kingdom, where they play diverse roles in the nervous system. Analysis of neuropeptide function in inverte- brates offers the opportunity to rapidly identify and assess the roles of multiple neu- ropeptides utilizing cellular, electrophysiological, and genetic techniques. The recent completion of the genomic sequence in the nematode Caenorhabditis elegans offers the opportunity to identify and characterize these signaling molecules using both forward and reverse genetic techniques. Analysis of FMRFamide (Phe-Met- Arg-Phe-NH 2 ) and related peptides (FaRPs) in C. elegans exemplifies this approach. Although initially isolated as a cardioactive agent from clams, 1 FaRPs have now been found throughout the animal kingdom 2–9 [for review, see Ref. 10], where they have many physiological functions [for reviews, see Refs. 10 and 11], including muscular control, 10,12 cardioregulation, 1,13–15 pain modulation, 4,16,17 and learn- a C. Li and A. Hart contributed equally to this article. All correspondence regarding flp genes should be directed to C. Li (li@bu.edu). Correspondence regarding nlp genes should be directed to A. Hart (hart@helix.mgh.harvard.edu). c Current address: New England Biolabs, Beverly, MA 01915. f Address for correspondence: MGH Cancer Center, 149-7202 13th Street, Charlestown, Mas- sachusetts 02129. (617) 726-5618 (voice); (617) 726-5637 (fax).