Biology Reference
In-Depth Information
between
daf
-
12
and
lin
-
42
in which they regulate one another's activity.
Notably, yeast two-hybrid experiments reveal that LIN-42 interacts with
a portion of the DAF-12 LBD and hinge (
Tennessen et al., 2010
).
A simple model is that LIN-42 inhibits DAF-12 dauer promoting activity,
perhaps by displacing DIN-1 corepressor or other coregulators. Interest-
ingly, a similar antagonism of nuclear receptor activity by Period operates
in mammals. Mammalian Period2 protein interacts with the adipogenic
nuclear receptor PPAR
g
, and inhibits its recruitment to target promoters.
Deletion of Period2 results in upregulation of PPAR
g
target gene expression
and adipogenesis (
Grimaldi et al., 2010
). Similarly, another regulator in the
circadian clock, the cryptochromes, interact with the glucocorticoid recep-
tor and inhibit its activity (
Lamia et al., 2011
). However, it remains to be
seen whether DAF-12 and LIN-42 work through a similar biochemical
mechanism.
3.7. Dauer reprogramming
An extraordinary finding over the last few years is that differentiated cells in
metazoans can be reprogrammed to earlier pluripotent fates (
Takahashi &
Yamanaka, 2006
). Interestingly,
C
.
elegans
can also reprogram temporal fates
when development is channeled through the dauer stage or by starvation.
Basically, mutants of multiple heterochronic loci, precocious or retarded,
exhibit near wild type like development when worms traverse the dauer
stage, revealing that mid-larval temporal fate transformations can be
prevented or even remodeled (
Euling & Ambros, 1996; Liu & Ambros,
1991
). The molecular basis of this reset is still obscure, but likely involves
daf
-
12
and dauer signaling pathways shutting down the heterochronic timer
during the dauer diapause (
Bethke et al., 2009; Hochbaum et al., 2011
). Pre-
sumably upon dauer exit, development is reinitiated using a different spec-
trum of regulators. Indeed, Karp and Ambros recently showed that a
remodeling of the regulatory activity of the
lin
-
4
and
mir
-
84
microRNAs
and associated factors affecting the
hbl
-
1
target gene occurs upon dauer exit,
resulting in a restoration of more normal temporal programming (
Karp &
Ambros, 2012
). Further studies in this area are bound to yield important
insights into this fascinating phenomenon.
3.8. Heterochronic genes and the molt cycle
Molting entails synthesis of the new skin and shedding of the old, and it is
important for the growth and maturation of many animals. The molt cycle
