Worm Breeder's Gazette 12(5): 46 (February 1, 1993)
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.
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 ( n676 n930 ).Both existing alleles, sel-10 ( ar28 )and sel-10 ( ar41 )only suppress the lin-12 ( n676 n930 )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]
Greenwald, I. S., Sternberg, P. W. and Horvitz, H. R. (1983). Cell 34, 435-444.
Larnbie, E. and Kimble, J. (1991). Development 112, 231-240.
Seydoux, G. and Greenwald, I. (1989). Cell 57, 1237-1245.