Worm Breeder's Gazette 13(5): 31 (February 1, 1995)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Dept. of Genetics, SK-50, University of Washington, Seattle, WA 98195
We have described unc-43 as a member of the Mac functional group involved in muscle activation (Reiner, Weinshenker and Thomas, this issue). Detailed behavioral analysis of unc-43 mutations revealed that it also has roles in processes other than muscle activation. The first observation is that loss-of-function mutations in unc-43 have defects in what we think of as motivational state. Mutant animals move in jerky fits and starts, interspersed with periods of no movement. We have also observed these jerky and lazy phenotypes for another Mac gene mutant, exp-2(sa26sd), and the partial exp-2 revertant exp-2(sa26sd sa67). We hypothesize that these phenotypes indicate a perturbation of the initiation of locomotion. The canonical unc-43(e408) loss-of-function mutation has been described as a progressive Egl, in contrast to other alleles. We outcrossed e408 and isolated a non-Egl e408 recombinant. We have designated the Egl mutation egl-(sa305). Another interesting phenotype of unc-43 was revealed in the following manner. We have been recording accurate ethological observations of percent enteric muscle activation per defecation cycle (percentEMC) in Mac mutants using a computer. The precision of this analysis and the collection of a large set of data have shown that there is a small but clear relationship between the defecation cycle period and constipation. We observed an inverse correlation between the degree of constipation (Con) and the length of the cycle period. Wild-type defecation cycles have a periodicity of approximately 45 seconds, while Con mutant cycle periods progressively shorten as animals become more Con, in severe cases to as short as 30 seconds. When constipation is relieved, either by an EMC or by passive release of the gut contents due to pressure, the cycle period returns to its normal value. We have assayed non-Mac mutants that are severely Con (e.g. aex-l) and observed the same phenomenon. The unc43(n498sd) semi-dominant mutation also confers a strong Con phenotype because of an EMC defect. However, the oscillation of the cycle period is much more extreme than in any other mutants that we have analyzed (from 25 seconds at the shortest to 85 seconds at the longest). As in other Mac mutants, the length of the cycle is related to the degree of constipation. We speculate that the hyper-oscillating periodicity of unc-43(n498sd) reveals a feedback mechanism from the gut to the defecation cycle clock, perhaps monitoring the degree of gut distention. We have also analyzed unc-43 loss-of-function mutations for defects in the defecation cycle. We found that unc-43 mutants also have an "echo" motor program that is activated 10-12 seconds after the activation of the principal motor program. This echo motor program is variably present, and is often somewhat incomplete (aBoc or Exp are frequently absent). This echo program has been previously described for the dec-8(sa200) mutation (Liu and Thomas, 1994). dec-8 maps near unc-43 and was also observed to be jerky and lazy, similar to unc-43 loss-of-function mutations. Therefore, we suspected that unc-43 and dec-8 were the same gene. The dec-8(sa200) mutation failed to complement unc-43(e266), and sa200 placed in trans to mDf7, which deletes unc-43, conferred an Unc phenotype like that of unc-43 loss-of-function mutations. Based on these results, we reassign sa200 as an allele of unc-43. We propose that sa200 is a weak, hypomorphic allele. It is difficult to determine whether the oscillating period of unc-43(n498sd) and the echo program of unc-43 recessive mutations reveal different aspects of the same mechanism, or coincidentally both affect the defecation cycle program through different mechanisms. In either case, we conclude that the unc-43 gene has an important role in both regulation of muscle activation and in control of the defecation motor program. WC Liu and J. H. Thomas (1994). J Neurosci 14: 1953-1962. p31