Worm Breeder's Gazette 7(2): 41
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.
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
below.
[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
fate.
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>
n379.
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.