aex mutants show an abnormal defecation. The defecation motor program is achieved by periodic activation of a stereotyped sequence of three muscle contractions: posterior body muscle contraction (pBoc), anterior body muscle contraction (aBoc) and expulsion (Exp). All aex mutants cause defects in both aBoc and Exp steps, but not in pBoc(1). Two GABAergic motor neurons, AVL and DVB, control the aBoc and Exp steps. These two neurons are stained by antibodies against GABA(2). Killing these neurons with a laser microbeam eliminates aBoc and Exp.
unc-25 mutants, deficient in GABA, show an Aex phenotype. These observations indicate that AVL and DVB are excitatory GABAergic motor neurons for the muscle contractions and that aex genes function on this unusual GABAergic pathway. So far only the
aex-3 gene was molecularly characterized among six aex genes. We would like to understand this pathway and have started characterizing other aex mutants. We firstly examined various phenotypes of these aex mutants in detail; defecation, body thrashing, pharyngeal pumping and pharmacological sensitivities to both aldicarb and levamisole. For defecation, all the aex mutants exhibit aBoc and Exp at a very low frequency as reported(1). Most mutants showed significantly faster defecation cycle periods (about 36 seconds) than the wild type (44 s), but the
aex-2 mutant showed the cycle close to the wild type. In general, constipated mutants tend to have shorter cycles than the wild type probably because of feedback inputs in the pathway. The
aex-2 mutant may be defective in this feedback. As for the pharmacological sensitivity, all the mutants showed resistance to the inhibitor of acetylcholinesterase aldicarb by a locomotion assay, suggesting that they have defects in the acetylcoline transmission as well as the GABA transmission for defecation. Furthermore, only the
aex-4 mutant showed strong resistance to the acetylcholine agonist levamisole suggesting that the
aex-4 mutant is defective in a postsynaptic step. We have initiated the cloning of
aex-1 to understand the molecular mechanism of this pathway. In the defecation behavior,
aex-1 mutants showed the most severe Aex phenotype among all aex mutants. Also,
aex-1 males showed a low mating efficiency although their locomotion appears to be normal. These males may also have defects in neurons for mating.
aex-1 have been mapped near the
lin-10 on Chromosome I by J. Thomas(1). The
aex-1 interval on the physical map is covered by only 11 cosmids. We are attempting a rescue experiment of
aex-1 mutants using these cosmids. (1) Thomas, J. H. (1990) Genetics 124: 855-872. (2) Mclitire, S. L, et al. (1993) Nature 364: 337-341.