Date of Award
Master of Science (MS)
Rhythmic behaviors are ubiquitous phenomena in plant and animal phyla. Ultradian rhythmic behaviors occur with a period of less than 24 hours and include such rhythmic behaviors as the beating of the heart and peristalsis in the gut. The nematode C. elegans exhibits three well-characterized ultradian rhythmic behaviors: ovulation, pharyngeal pumping, and the defecation motor program (DMP). The DMP occurs every ~45 seconds in wild-type worms and comprises three distinct muscle contractions: a posterior body contraction (pBoc), an anterior body contraction (aBoc), and an enteric muscle contraction (Emc), which is coupled to expulsion (Exp). The rhythmicity of the DMP is Ca2+-dependent, meaning fluctuations in intracellular Ca2+ levels in the pacemaker cell regulate the behavior. A forward genetic screen was performed to identify genes necessary for proper pacemaker function (Iwasaki et al., 1995). One of the mutants isolated, dec-11, lacks pacemaker activity and displays long and irregular defecation cycles. However, the gene mutated in dec-11 worms has not been identified. In order to determine the function of the dec-11 gene in the control of pacemaker activity for the DMP, genetic analysis and video microscopy were utilized. First, genetic analysis was performed to test whether dec-11 acts upstream of IP3 mediated Ca2+ release using mutations in ipp-5 and lfe-2, which encode an IP3 phosphatase and an IP3 kinase respectively. dec-11;ipp-5 and dec-11;lfe-2 double mutants both showed partial suppression of the irregular defecation cycle phenotype characteristic of dec-11 single mutants. Additionally, when dec-11 worms were grown on high Mg2+ plates, the irregular defecation cycles were suppressed, suggesting a role for dec-11 in the regulation of the DMP. Parallel work using SNP interval mapping and whole-genome sequencing has allowed us to identify a molecular interval in which dec-11 is located and to generate a list of candidate genes. Additionally, RNAi analysis of candidate genes will allow us to determine the molecular identity of dec-11. Taken together these data are consistent with a model that places the function of dec-11 in the regulation of the initiating event of the DMP.