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.

unc-43 Pleiotropies Imply Both Neuronal and Muscular Sites of Function.

David J. Reiner, 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
WC Liu and J. H. Thomas (1994). J Neurosci 14: 1953-1962.