Biology Reference
In-Depth Information
the relative contributions of these interactions to DAF-12 functions. Also of
key relevance are miRNA targets of DAF-12, notably the
let-7
family
miRNA genes. Ligand bound DAF-12 moderately activates
let-7
family
miRNAs during continuous development, and, for at least
mir-84
and
mir-241
, this regulation appears direct, resulting in promotion of L3 fates
through repression of HBL-1 levels (
Bethke, Fielenbach, Wang,
Mangelsdorf, & Antebi, 2009; Hammell, Karp, & Ambros, 2009
).
Ligand-free DAF-12, in contrast, is a potent repressor of these miRNAs
in dauers, suspending their ability to program stage transitions upon dauer
entry. Not only are these miRNA genes targets of DAF-12, but repression
of DAF-12 levels during the L3 stage is achieved through feedback targeting
of
daf-12
mRNAs by the
let-7
family miRs, regulation that is necessary for
proper developmental progression.
10. INTERRUPTED DEVELOPMENT: REPROGRAMMING
AND RESYNCHRONIZATION
An unexpected phenomenon was revealed when heterochronic
mutants progressed through the dauer larval stage. Certain heterochronic
mutants come out of the dauer stage appearing developmentally normal
and are able to lay eggs and mate (
Abrahante et al., 2003; Euling &
Ambros, 1996; Liu & Ambros, 1991
). However, only those mutants whose
defects begin early, in the L1 or L2, are subject to this postdauer suppression.
Mutants whose developmental defects appear late in development, such as
lin-29
mutants, are not suppressed by going through dauer. But regardless of
whether the mutant would have ceased molting precociously after the third
stage, or whether it would have continued molting after the fourth stage, all
of these suppressed postdauer mutants undergo exactly two molts after
emerging from the dauer (
Fig. 6.4
). This phenomenon implies the existence
of a molecular mechanism for setting developmental time that is indepen-
dent of the early-acting heterochronic genes.
This reprogramming of cell fates upon passage through the dauer is seen
more vividly in the hermaphrodite vulva (
Euling & Ambros, 1996
). Because
dauer larvae arrest midway through larval development, precocious vulva
development sometimes gets caught in process when the dauer arrest occurs
(
Fig. 6.4
). Remarkably, when the animal emerges from the dauer it develops
a perfectly normal vulva, but not in the way that one would expect: it does
not simply pick up where it left off. Normally, three of six VPCs divide mul-
tiple times to generate the 22 cells of the vulva. In precocious mutants that
