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.
|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.