Worm Breeder's Gazette 14(2): 67 (February 1, 1996)
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 | Division of Biology and Howard Hughes Medical Institute, Caltech, Pasadena, CA, 91125 |
| 2 | Present address: Department of Biochemistry University of Kentucky Medical Center, 800 Rose Street, Lexington, KY, 40536-0084. |
The Pn.p cells adopt fates that correlate with their relative position along the anterior-posterior body axis: the more anterior cells, P(1,2).p, and the more posterior cells, P(9-11).p, fuse with the epidermis during L1. The central 6 Pn.p cells, P(3-8).p, remain unfused though L2 and are competent to adopt vulval fates in response to an inductive signal, LIN-3, produced by the anchor cell. We have examined the role of HOM-C genes in regulating the competence of this central group. These central cells can adopt one of two vulval fates, denoted 1' or 2'. Cells that do not adopt a vulval fate divide once and fuse with the epidermis, adopting a non vulval fate, denoted 3'. In wild type, P3.p adopts either the 3' fate or a distinct non-vulval fate, denoted 4', in which it fails to divide and fuses with the epidermis. The wild-type pattern of fates is thus either 3'3'2'1'2'3' or 4'3'2'1'2'3'. Wang et al.[1] and Clark et al [2] demonstrated that lin-39 was expressed in the central Pn.p cells and was required to prevent the central 6 Pn.p cells from fusing during L1. Using the hypomorphic allele lin-39(n709) we have examined the influence of lin-39 on Pn.p cell response to inductive signal. In n709 animals P3,7,8.p often adopt the 4' fate while P(5-7).p are typically induced but frequently adopt fates characteristic of reduced sensitivity to inductive signal. Consistent with the idea that lin-39 might be required for normal response to inductive signal, n709 enhances the vulval defects seen in the weak Vul mutations lin-2(n768), lin-7(n308) and let-23(n1045). These results suggest that lin-39 plays at least two roles in Pn.p specification - an early role preventing fusion with the epidermis and a late role mediating competence to respond to inductive signal. mab-5 acts antagonistically to lin-39 in the regulation of Pn.p competence. Salser et al.[3] demonstrated that mab-5 was expressed in a posterior domain that included P7.p and P8.p but not the more central Pn.ps. Using a heat shock contruct expressing low levels of LIN-3, we observed that P7,8.p are less sensitive to LIN-3 than P6.p in gonad ablated animals. This difference is mediated by mab-5. Moreover, in animals bearing the weak gain-of-function mutation, let-23(sa62), central Pn.p cells are frequently induced to vulval fates in a cell autonomous manner but P8.p is only rarely induced. Again, this spatial pattern is dependent on mab-5 activity. Consistent with mab-5 expression making Pn.p cells less sensitive to inductive signal, the gf mutation mab-5(e1751), which causes expression of mab-5 in all central Pn.p cells strongly enhances the same weak Vul mutations that interact with lin-39(lf). By constructing double mutants between HOM-C genes and mutations that hyperactivate the inductive signalling pathway we have defined how lin-39 and mab-5 interact with the induction pathway. In particular, lin-39(n709) can suppress a gf mutation in let-60/Ras, let-60(n1046) , as well as a null mutation in lin-1, a downstream transcription factor and likely target of inductive signal regulation. mab-5(e1751) can also suppress let-60(n1046). These results are consistent with two models: either lin-39/mab-5 regulate downstream nuclear target(s) of the inductive signalling pathway or lin-39/mab-5 are themselves downstream targets. By generating a spatial pre-pattern of Pn.p competence the HOM-C genes may reinforce the characteristic precision of vulval patterning and play an important role in the evolution of the nematode vulva. [1] Wang, B.B., M.M. Muller-Immergluck, J. Austin, N. Tamar Robinson, A. Chisholm and C. Kenyon (1993). A homeotic gene cluster patterns the anteroposterior body axis of C. elegans. Cell 74:29-42. [2]Clark, S.G., A.D. Chisholm and H.R. Horvitz (1993). Control of cell fates in the central body region of C. elegans by the homeobox gene lin-39. Cell 74:43-55. [3]Salser, S.J., C.M. Loer and C. Kenyon (1993). Multiple HOM-C interactions specify cell fates in the nematode central nervous system. Genes Dev. 7:1714-1724.