Mutations in the gene
sel-10 were isolated in a screen for suppressors of the Egl phenotype caused by the hypomorphic
lin-12 allele
lin-12 (
n676n930).Both existing alleles,
sel-10 (
ar28)and
sel-10 (
ar41)only suppress the
lin-12 (
n676n930)Egl phenotype in combination with another linked background mutation(s) which we refer to as sel(arX). However, these
sel-10 mutations alone have strong effects on several specific cell fate decisions in
lin-12 mutants. In the anchor cell (AC)/ventral uterine precursor cell (VU) decision involving Z1 .pppand Z4 .aaa,
lin-12 spcifies the VU fate and is proposed to encode a receptor for the "AC-to-W signal" (Greenwald et al., 1983; Seydoux and Greenwald. 1989). In
lin12 (0)mutants, both Z1 .pppand Z4 .aaabecome ACs. In approximately 1/3 of
lin-12 (0);
sel-10 hermaphrodites, however, only one AC is formed (see Table); we infer that either Z1 .pppor Z4 .aaamust have adopted the W fate. Therefore,
sel-10 appears to bypass partially
lin-12 ,allowing
lin-12 (0Janimals to express a fate that is normally dependent on
lin-12 activity. One possible explanation of our results is that all three of the
lin-12 (0)alleles used encode products which can be stabilized or otherwise rendered functional by
sel-10 mutations. Assuming this is not the case, however, there are two general mechanisms by which
sel-10 may be acting:
sel-10 mutations may act downstream of
lin-12 in a linear genetic pathway to cell-autonomously trigger the W fate, or
sel-10 mutations may allow specification of the W fate through an altemative pathway. The observation that
lin-12 (0);
sel-10 animals never have O AC seems to argue against the former mechanism (thanks to Greg Beitel for pointing this out). One way to distinguish between these possibilities is to ask whether the W fate in
lin-12 (0);
sel-10 animals is still dependent on an AC-to-W signal, as it is in wild type, or whether the W fate can occur in the absence of cell communication, as it can in
lin-12 (0)mutants (Seydoux and Greenwald, 1989; Greenwald and Seydoux, 1990). We ablated either Z1 or Z4 (the precursors to Z1 .pppand Z4 .aaa,respectively) in
lin-12 (
n941);sel(arX)
sel-10 (
ar41)larvae, and asked whether the remaining Z1 .pppor Z4 .aaacell would express the AC or VU fate. The AC fate was expressed in all cases (n=24), indicating that the VU fate in such animals is still dependent on cell interactions. Therefore, either
sel-10 (
ar41)allows
lin-12 (
n941)protein to function, or
sel-10 (
ar41)activates an alternative pathway of cell communication which specifies the W fate. There is some precedent for thinking that there may be a non-
lin-12 -mediatedcell communication pathway which specifies the VU fate. Ablation experiments described by Savage et al. in this Gazette suggest that there may be another cell-signalling pathway which normally specifies the W fates of Z1 .ppaand Z4 .aap,since the ability of Z1 .ppaand Z4 .aapto adopt an AC fate increases after ablation of Z1 .pppand Z4 .aaaeven in a
lin-12 (d)background. Possibly,
sel-10 mutations might allow that other pathway to be recruited to specify the VU fate of Z1 .pppor Z4 .aaa. One obvious model is that the postulated alternative pathway involves
glp-1 ,a gene which is both structurally and functionally related to
lin-12 .In an attempt to test this model, we made a
lin-12 (
n941)glp-l
(q46 );
sel-10 (
ar41)triple mutant. However, since such animals were still Lag L1 arresters (the
lin-12 glp-1 double mutant phenotype described by Lambie and Kimble, 1991), we could not determine if
sel-10 (
ar41)requires
glp-1 activity in order to suppress the 2 AC phenotype. Several other effects of
sel-10 mutations are likely to be relevant. First, the combination sel(arX)
sel-10 (
ar41)weakly suppresses the maternal-effect lethality caused by
glp-1 (
e2142 )at 25 or
glp-1 (
q231 )at 20 . Possibly, this could reflect an increase in
glp-1 expression or activity caused by
sel-10 .Alternatively,
sel-10 mutations may bypass the need for
glp-1 activity in the early embryo just as they may bypass the need for
lin-12 activity in the AC/VU decision, by activating some alternative pathway.
sel-10 mutations also enhance
lin-12 (d)alleles:
sel-10 (
ar41)increases the penetrance of the O AC phenotype in
lin-12 (
n379)/+animals from 17% to 96%, and causes normally Vulvaless
lin-12 (
n379)or
lin-12 (
n302)animals to be Multivulva Fmally, another intriguing effect of
sel-10 mutations is that they cause maternal-effect lethality in the background of
lin-12 (d)mutations: embryos from
lin-12 (
n302);
sel-10 (
ar41)mothers undergo many rounds of cell division but do not appear to elongate. One hypothesis is that this may be a "
glp-1 (d)"-likephenotype. Reversion of this maternal-effect lethality may identify supprcssor mutations in genes which interact with
lin-12 and
glp-1 ,or which function in the postulated alternative pathway. [See Figure]