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.

HOM-C genes and vulval fate specification

Thomas R. Clandinin1, Wendy S. Katz2, Paul W. Sternberg1

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

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.