Worm Breeder's Gazette 7(2): 41

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The lin-12 Locus May Determine Cell Fates within Equivalence Groups

I. Greenwald, P. Sternberg, C. Ferguson, B. Horvitz

Figure 1

In a previous Newsletter [6(1): 40, 1981], we described several 
classes of mutations affecting vulva development that mapped to the 
lin-12 III locus.  We have continued characterizing these and other 
lin-12 mutations genetically and anatomically.  We now think that lin-
12 acts as a binary switch during development to determine the 
expression of alternative cell fates in a number of different tissues.
The studies of Sulston and White (1980) and Kimble (1981) have shown 
that, although laser ablation of most cells does not affect the fates 
of other cells, in a few cases the ablated cell is replaced, i.e.  a 
neighboring cell (which normally adopts the '2  fate') adopts the fate 
of the ablated cell ('1  fate').  Because cells that normally adopt 
the 2  fate have the potential to adopt the 1  fate, such cells are 
considered to belong to an 'equivalence group.'  That cell fate is 
altered after laser ablation implies that interactions among the cells 
of an equivalence group define the normal developmental program.  
Presumably these interactions affect the expression of genes that 
determine cell fate.  We think that lin-12 is one such gene.
Mutations in lin-12 affect the fates of the cells of the gonadal and 
ventral hypodermal equivalence groups; the mesoderm is similarly 
affected, suggesting that certain M cell progeny may be members of an 
equivalence group.  We have examined the effects of three different 
classes of lin-12 mutations on these tissues.  Two of these classes, 
lin-12(Muv) and lin-12(Vul), comprise semidominant mutations that by 
genetic criteria appear to result in the expression of elevated levels 
of lin-12 activity.  One class, lin-12(0), comprises recessive, 
putative null alleles that lack lin-12 activity.  The semidominant 
mutations result in discrete transformations that are opposite to the 
transformations caused by the lin-12(n) alleles, as shown in the table 
[See Figure 1]
We described most of the semidominant alleles of the lin-12(Muv) and 
lin-12(Vul) classes in the previous Newsletter.  Hermaphrodites that 
are homozygous or heterozygous for lin-12(Muv) alleles (n137, n177, 
and n427) have a multivulva phenotype resulting from the abnormal 
divisions of the cells of the vulval equivalence group.  Note that 
these cell divisions are anchor cell (ac)-independent in lin-12(Muv) 
mutants; in wild-type hermaphrodites, the required for the induction 
of vulval cell divisions (Kimble, 1981).  In lin-12(Vul) mutants (n379,
n302, and n676), some ac-independent Pn.p cell ac is divisions occur 
but the alleles differ with respect to the frequency and extent of 
divisions; the most severe allele is n676, which as a heterozygote is 
generally vulvaless but as a homozygote shares some characteristics of 
the lin-12(Muv) mutants.  For the gonadal and ventral hypodermal 
equivalence groups, it appears that the extreme semidominant mutations 
[the lin-12(Muv) class] result in the transformation of cells to the 2 
We have generated over 40 lin-12(0) alleles by reversion of n137, 
n302, and n676.  Viewed through the dissecting microscope, some lin-12(
0) animals appear very scrawny, but others are of relatively normal 
size: hermaphrodites are sterile and have a large protrusion in the 
normal vulval position (they often explode as young adults), and males 
have abnormal tails.  The lin-12(0) alleles in both the hermaphrodite 
and male result in the transformation of cells of the gonadal 
equivalence group to the 1  fate.  The cell fates of the ventral 
hypodermal precursor cells indicate that the absence of lin-12 
activity need not result in the expression of the 1  fate.  In the 
ventral hypodermal equivalence groups, the three fates--1 , 2 , and 3 -
-can be distinguished based on cell lineages.  The fate of P9.p in lin-
12(0) males is 3 , not 1 .  The hermaphrodite P(3,4,8).p cells, 
although variable, also demonstrate this point.
By examining various heterozygous combinations of lin-12 mutations 
for the number of pseudovulvae and the frequency of functional vulva 
formation, we have inferred that the semidominant alleles result in 
the ectopic expression of lin-12.  We can rank the various classes of 
alleles, by order of decreasing degree of ectopic expression, as lin-
12(Muv)> l)> > .
Within the lin-12(Vul) class, we can rank the alleles as n676> n302> 
We postulate that in wild-type development, cell-cell interactions 
result in the expression of a high level of lin-12 in certain cells, 
causing them to adopt the 2  cell fate.  In other members of the 
equivalence group, we would expect the level of lin-12 activity to be 
low.  In the gonadal equivalence groups, this low level of activity 
appears to be sufficient to result in the expression of the 1  fate.  
However, a low level of lin-12 activity is not sufficient for 
expression of the 1  fate in the ventral hypodermis, implying that 
other genes affect the determination of cell fate in this tissue.

Figure 1