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Zygote
FIGURE 4.2
Complete lineage of C. elegans hermaphrodite. (Based on Sulston et al., 1983)
produced by a cell called Q. In wild-type animals, Q
divides into two daughter cells, Ql.a and Ql.p (Figure
4.3A). Both of these cells divide once more, but only Ql.p
produces a touch cell. The unc-86 gene is turned on only
in the Ql.p. and a mutation in unc-86 (Figure 4.3B)
results in the “transformation” of Ql.p into a cell that
behaves like its mother, Q. We call this cell Q'. This trans-
formed cell continues to divide, producing Q1.a' and
Q1.p', but in the continued absence of unc-86 function,
the Q1.p' transforms into Q”, which continues to behave
like its mother Q' and its grandmother Q. Thus,
mutations in unc-86 affect the lineage of touch cells;
mechanosensory neurons are never born in these
mutants.
Another gene uncovered in Chalfie's screen of touch
mutants is named mec-3. In these mutants (Figure
4.3C), the cells that would be touch sensitive are born,
but they do not differentiate into mechanosensory
neurons. Instead, they turn into interneurons. Thus, the
mec-3 mutation affects neural subtype determination.
The mec-3 gene codes for a transcription factor that is a
member of the LIM-homeodomain family. Interest-
ingly, the transcription of the mec-3 transcription factor
is directly regulated by the unc-86 transcription factor.
Cells fated to become touch cells all express unc-86 at
first, and this transcription factor binds to the regula-
tory sequence of DNA that controls the transcription of
the mec-3 gene. Thus, unc-86 mutants do not express
mec-3. However, in normal animals, the protein UNC-
86 leads to the expression of MEC-3, and when these
two proteins are expressed in the same cell (the cell that
will become a mechanosensory neuron), they physi-
cally interact to make a heterodimeric transcription
factor with new specificity that activates genes that
neither MEC-3 nor UNC-86 can activate on their own.
Several of these are defined by mutations in other
genes that cause touch insensitivity, such as the mec-7,
mec-12, and mec-17 genes. These three genes encode
proteins that are used in the differentiation of the spe-
cialized touch cell cytoskeleton (Figure 4.3D). This
system provides an excellent example of a simple hier-
archical cascade of transcription factors, one regulating
and interacting with the next, the end result of which is
to turn on genes that the cell uses to realize its fate.
Using a genomic approach, Chalfie and colleagues
(Zhang et al., 2002) have tried to find even more genes
involved in the touch cell pathway by looking for dif-
ferences in profiles of all expressed genes in normal
animals versus mec-3 mutants. This approach identi-
fied up to 50 more genes in the pathway downstream
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