In the course of mapping
gm17, an HSN-migration defective mutant isolated by Michael Basson in the Horvitz lab, we discovered that it fell under mnDp57(X) and had a similar appearance to
dpy-23(
e840) (a dumpy body with characteristic bulges around the head).
e840 failed to complement
gm17 for the Dpy phenotype; in addition,
e840 has an HSN migration defect. Anti-serotonin antibody staining to observe HSN morphology showed that the HSNs migrated 53% and 46% of normal their normal distances in
gm17 and
e840 animals, respectively. The HSN axons, which normally extend forward to the pharyngeal nerve ring, extend rearward to the tail in 25% of
gm17 animals and 40% of
e840 animals. Many HSN cell migration mutants also have mild HSN axon defects, presumably because the cell body is in the wrong place relative to axon guidance cues. The
dpy-23 axon defects, however, appear to be more severe and of higher penetrance than those usually observed in cell migration mutants. Nomarski optics showed that the QL cell, which normally migrates rearward, often migrated forward instead. Finally, the gonad arms frequently have abnormal reflexions, indicating a distal tip cell migration defect. The dumpy phenotype of
dpy-23 animals can be maternally rescued. Examination of the HSNs of mutant progeny of heterozygous animals by Nomarski and anti-serotonin staining showed that the HSN migration defects were also usually maternally rescued. We found several animals with HSN cell bodies in the correct positions but that still had extended HSN axons rearward to the tail. This suggests that
dpy-23 is specifically required for proper HSN axon guidance, and that the misrouted axons are not simply a secondary result of misplaced cell bodies. Because
dpy-23 mutants are very sick, and because in the past it has been suggested that
dpy-23 might be involved in dosage compensation, we were concerned that
dpy-23s effects on cell migrations might be caused by defects in dosage compensation, by a Dpy body shape, or by general sickness. The cell bodies, however, are not misplaced in dosage compensation Dpy genes like
dpy-21 or
dpy-28. Furthermore, other sick Dpy mutants, such as
dpy-22 or
unc-119, do not have HSN migration defects. Efforts to clone
dpy-23 are in progress. We have mapped
dpy-23 relative to RFLPs, and have achieved single-cosmid rescue. We are now further narrowing down the rescuing region.