Worm Breeder's Gazette 14(1): 54 (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.

The First Orthogonal Turn of the Migrating Distal Tip Cells of C. elegans is Regulated by Cell-autonomous Expression of the UNC-5 Guidance Receptor.

Ming-Wan Su1, Youwen Zhou1, Jim Kramer2, Ed Hedgecock3, Joe Culotti1

1 S. Lunenfeld Res. Inst., Mt. Sinai Hospital, Toronto, Canada
2 CMS Biology, Northwestern U. Med. Sch, Chicago
3 Biology, Johns Hopkins U., Baltimore, Maryland

     The distal tip cells (DTCs) in C. elegans migrate along a
complex trajectory comprising three linear phases punctuated by two
orthogonal turns. They are born at ventral midbody near the region
of the presumptive vulva, migrate along the ventral body muscles in
opposite directions away from this region (phase 1). In the early
L4 they turn orthogonally and migrate on the basal surface of the
epidermis towards the dorsal side (phase 2). When they reach the
dorsal side they turn orthogonally again and migrate towards
midbody along the dorsal body muscles (phase 3). This migratory
program continues in mutants like unc-5,6,40 which fail to execute
the second migratory phase, but which execute the first and third
phases of the migration with approximately normal  timing. It also
continues in mutants like dig-1 and mig-4 in which the gonad
primordium is displaced, suggesting that position of the DTC does
not determine when it turns, rather, turning is triggered by a
timing mechanism that acts globally. Adam Antebi and E.H. have
described alleles of daf-12 and of mig-8 that appear to affect this
timing mechanism, preventing the DTCs from executing any turns (WBG
13#3, p.85).
      UNC-5 is required for dorsal to ventral (phase 2) migrations
of the hermaphrodite DTCs. The spatial and temporal expression
pattern of reporters driven by the unc-5 promoter have been
previously described (1993 Abstracts, pp. 429-430). The unc-5-
reporter constructs were found to express precisely at the
beginning of the first orthogonal turn of the DTCs in the wild
type. unc-5 also expresses in unc-5, 6, 40, dig-1, and mig-4
mutants with the correct timing, but fails to express in mig-8 and
certain daf-12 mutants. These results suggest that unc-5 expression
in the DTCs, regulated by daf-12 and mig-8, is causal for their
first orthogonal turn. When expressed, UNC-5 responds to a pre-
existing gradient of the underlying UNC-6 path cue molecule by
reorienting the cell along the D/V axis and guiding it towards the
dorsal side.
     We have tried to express unc-5 precociously in the DTCs to
further test this hypothesis. The emb-9 collagen gene expresses in
the DTCs early during the first longitudinal phase of their
trajectory. In animals co-transformed for emb-9-unc-5 and emb-9-
lacZ, but not in control emb-9-lacZ animals, the DTCs migrate
precociously toward the dorsal side at an oblique angle, suggesting
that they can execute phase 1 and phase 2 processes concomitantly.
This precocious turning occurs even when the emb-9-unc-5, emb-9-
lacZ array is passed into unc-5(e53) or daf-12(rh84) mutants, but
fails to occur in unc-6(ev400) mutants. These results demonstrate
that cell-autonomous expression of unc-5 in the DTCs is causal for
their first orthogonal turn. Apparently, this expression, hence the
first turn, is regulated by a timing mechanism requiring daf-12 and
mig-8 for its execution.