Journal of Neuroscience, Vol 15, 6094-6102, Copyright © 1995 by Society for Neuroscience
Reversal of a muscle response to GABA during C. elegans male development
DJ Reiner and JH Thomas
Department of Genetics, University of Washington, Seattle 98195, USA.
In the C. elegans hermaphrodite the expulsion step of defecation depends on
the coordinated contraction of three enteric muscle groups: the anal
depressor muscle, the intestinal muscles, and the sphincter muscle. These
muscles are activated by excitatory GABA neurotransmission. Mutations in 13
genes that affect activation of these enteric muscles have previously been
identified. We show that the larval male defecates by contracting the same
set of enteric muscles, and that these contractions require 12 of these 13
genes. However, near the end of the last larval stage, the male anal region
undergoes a developmental change, including dramatic hypertrophy of the
anal sphincter muscle and the opening of a cloacal canal. We find that this
modified sphincter must now relax to permit defecation. In contrast to the
larval male, we find that in the adult male only 2 of the 13 genes required
for enteric muscle contraction, unc-25 and unc-47, are important for
sphincter muscle relaxation. unc-25 and unc-47 are required for the
synthesis and utilization of GABA. We also find that two other genes,
unc-46 and unc-49, previously implicated in the inhibitory action of GABA
on body-wall muscle, are also required for normal adult male sphincter
relaxation. In these mutants, failure to relax the sphincter muscle results
in a constipated phenotype, and killing the sphincter muscle rescues this
phenotype. We also find that a GABA agonist or GABA itself can suppress the
adult male sphincter relaxation defect of unc-25 mutants.(ABSTRACT
TRUNCATED AT 250 WORDS)