Biology Reference
In-Depth Information
Rougvie, 1999
).
lin
-
42
controls developmental timing, molting, and
dauer formation, and it works in opposition to
daf
-
12
for some of these pro-
cesses. In developmental timing circuits,
lin
-
42
loss-of-function mutants dis-
play precocious phenotypes, most conspicuously around the L3 molt, when
they exhibit precocious seam cell fusion and adult alae formation. These
studies suggest that
lin
-
42
prevents early expression of adult fates. Addition-
ally, mutants show earlier defects in the L2 stage in certain genetic back-
grounds, suggesting that it works at multiple steps (
Abrahante, Miller, &
Rougvie, 1998
).
lin
-
42
and
daf
-
12
display intriguing genetic interactions, which suggest
they antagonize one another's activity. As mentioned earlier,
daf
-
12
mutants
repeat L2-proliferative divisions of the seam cells at the L3 stage:
lin
-
42
mutation reverts this phenotype, restoring seam cell number back to normal
(
Tennessen, Gardner, Volk, & Rougvie, 2006
). Likewise,
daf
-
12
mutation
counteracts the
lin
-
42
precocious expression of adult seam fates. Similar
countervailing interactions are seen in gonadal developmental timing cir-
cuits. Whereas
lin
-
42
mutants cause precocious dorsal migration of the distal
tip cells in the L2, one full stage earlier than normal,
daf
-
12
(
rh61
) mutants
cause delayed gonadal distal tip cell migration. In
lin
-
42
;
daf
-
12
double
mutants this migration is nearly normal or delayed, depending on the allele
(
Fielenbach et al., 2007; Tennessen et al., 2006
).
lin
-
42
also opposes
daf
-
12
activity with respect to dauer formation
(
Tennessen, Opperman, & Rougvie, 2010
).
lin
-
42
mutants inappropriately
enter the dauer stage at moderately elevated temperatures, suggesting that
lin
-
42
(
) normally prevents dauer entry and promotes reproductive devel-
opment under mild stress. Consistent with this notion,
lin
-
42
expression
drops as animals enter the dauer stage. Genetic epistasis experiments suggest
lin
-
42
works downstream of IIS and TGF-
b
, coincident with
daf
-
12
.
Specifically
daf
-
12
Daf-d null mutants suppress the
lin
-
42
Daf-c defect.
Moreover,
lin
-
42
(
þ
) overexpression prevails over the Daf-c phenotypes
of
daf
-
9
/CYP27A1 mutants as well as
daf
-
12
LBD mutants, placing it at
the same step as steroidal signaling. This latter finding is quite striking
because it implies that
lin
-
42
overexpression can drive reproductive devel-
opment in the absence of the DAF-12 ligands, rendering the receptor ligand
independent.
Currently it is unknown how
lin
-
42
and
daf
-
12
affect one another's
activity. The molecular basis of the yin-yang behavior could result from a
convergence of parallel antagonistic pathways on the same target genes.
Another possibility is that there exists a more intimate physical interaction
þ
