Recent developments suggest that
eat-12 plays an important role in muscle contraction.
eat-12 was originally defined by one semidominant allele,
ad695 .
ad695 is slightly Dpy, completely male-mating defective (possibly because the spicules are often protruded), and moderately Eat, because the relaxation of the terminal bulb of the pharynx is delayed in some pumps (Avery 1993, Genetics 133: 897). Recently we found a new mutation that causes an
ad695 -1ikephenotype,
n2368 ,in a screen for dominant suppressors of
egl-1 (
n986 ),which causes the HSNs to undergo programmed cell death in hermaphrodites. We subsequently found that
n2368 does not suppress the HSN deaths, but rather causes the vulval muscles to contract in the absence of the HSNs, leading to an HSN-independent egg-laying constitutive (Egl-c) phenotype. We suspect that
n2368 is allelic to
ad695 because
n2368 affects all the phenotypes affected by
ad695 ,but to a greater extent, and maps close to
ad695 (between
bli-6 and
unc-24 ).To check whether
ad695 worms are also Egl-c we staged the most developed embryo in each of several
ad695 gravid adults by counting the number of nuclei. The oldest embryos retained by
ad695 worms had 7.6 1.8 nuclei (mean se, n=8). In contrast, each of four wild-type worms retained embryos with more than 20 nuclei. This result suggests that eggs of earlier stages are laid by
ad695 mutants. Thus
ad695 ,like
n2368 ,causes an Egl-c phenotype. However, unlike
n2368 ,
ad695 doesn't suppress
egl-1 ,perhaps a reflection of its weaker phenotype. The semi-dominance of
ad695 and
n2368 suggested they might be gain-of-function (gf) mutations. We reasoned that loss-of-function (If) mutations might be egg-laying-defective (Egl-d). Since extensive screens for Egl-d mutants have been carried out previously (e.g., Trent et al. 1983, Genetics 104: 619), it seemed possible that If mutations had already been found.
egl-19 (
n582)in particular has a map position consistent with that of
ad695 ,and it is Lon and Unc (slow and floppy). We further noticed that
n582 worms are slightly Eat; the terminal bulb has occasional brief, partial contractions, a phenotype opposite to that of
ad695 and
n2368 .Furthermore, we have mapped
n582 within 0.2 mu (95% confidence interval) of
ad695 .The phenotypic resemblance between
ad695 and
n2368 ,the opposite phenotypes of
n582 from those of
n2368 and
ad695 ,and the close genetic linkage between
ad695 and
n582 together suggest that the three mutations are allelic. If these three mutations are indeed allelic, the gene
eat-12 /egl-19 may play a pivotal role in the control of muscle contraction, since opposite mutations have opposite effects on terminal bulb, vulval, and possibly body wall muscle contraction. Furthermore, since the Egl-d phenotype of
n582 is insensitive to serotonin (Trent et al. 1983, Genetics 104: 619) and
n2368 vulval muscles are capable of contracting without HSNs, it seems likely that these mutations affect the muscle itself, not the nervous system. We have failed to detect structural defects in the muscles of these three mutants under polarized light. We therefore suspect that the defects may be at the level of membrane excitability or excitation-contraction coupling.