Throughout evolution the Hox genes are responsible for establishing regional identity in the antero-posterior axis. In the ventral midbody of C. elegans the Hox gene
lin-39 specifies which of the Pn.p cells will become vulval cells, and which of them will fuse to the hypodermis.
lin-39 activity is necessary both at the L1 stage [for P(3-8).p] and later, at the L3 stage [for P(5-7).p] in order for the cells to remain unfused and to be further induced to form the vulva [1]. In
lin-39 (-) mutants all the Pn.p cells undergo fusion leading to a vulvaless phenotype (Vul). In P. pacificus the activity of
lin-39 is also needed for vulval fates but lack of this activity results not in cell fusion but rather in programmed cell death. This regulation is achieved by the repressive activity of
lin-39 on the apoptotic effector
ced-3 [2] . We have asked whether cell fusion of Pn.p cells in C.elegans is regulated in the same manner through repression of a 'fusion effector'. Albeit the importance of the Hox gene regulation, there are almost no identified Hox target genes that participate in actual cellular events including cell fusion. We isolated
eff-1(
hy21) ( e pithelial f usion f ailed ) , a mutant in which all epithelial cells fail to fuse. Our results suggest that
eff-1 may be the first isolated gene in C.elegans encoding a fusogen- a protein that mediates cell-cell fusion [3]. The vulva in
eff-1(
hy21) single mutants is functional even though cell fusion during vulva formation is defective. In order to test whether
eff-1 could serve as the 'fusion effector' regulated by
lin-39, we investigated worms that are marked at their adherens junctions by the JAM-1:GFP construct. We found out that in
lin-39(
n1760);
eff-1(
hy21) double mutants lack of
eff-1 activity completely suppressed the Vul phenotype of
lin-39(-) . This was evident at the L1 stage as all the Pn.p cells in the double mutant escaped fusion to the surrounding hypodermis and also at the L3 stage as the Pn.p cells remained unfused and continued proliferating to form the vulva primordium. Thus,
lin-39 inhibits cell fusion in C. elegans by repressing the fusogenic activity of
eff-1 in the vulva equivalence group. To test whether the role of
lin-39 in vulva formation is restricted to fusion repression, we analyzed the vulva structure formed in the
lin-39(
n1760);
eff-1(
hy21) double mutants. Although the vulval cells were able to migrate and form a stack of rings in the double mutant, the final structure of these rings was completely abnormal leading to a non-functional vulva in contrast to the vulva of
eff-1(
hy21) single mutants. Thus, lin- 39 activity is required not only for inhibiting the fusion of vulva precursor cells, but also for induction of proper vulva organogenesis. We will discuss our studies on the relationship between
eff-1 and
lin-39 as well as other Hox genes in C. elegans and our experiments with worms carrying hs-
lin-39 constructs in order to test directly LIN-39 inhibition of
eff-1(
hy21) activity. [1] Maloof and Kenyon (1998) Development 125 : 181 [2] Sommer et al. (1998) Development 125: 3861 [3] Shemer et al. (2001) 13 th International C. elegans meeting [4] Mohler et al. (2001) 13 th International C. elegans meeting