Worm Breeder's Gazette 14(1): 50 (October 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.

Cell and Axon Migrations are Misdirected in dpy-23 Mutants

Paul Baum, Gian Garriga

Department of Molecular and Cell Biology, University of California Berkeley, CA 94720

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-23¹s 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.