unc-43 pleiotropies imply both neuronal and muscular sites of function David J. Reiner and James H. Thomas 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