Biology Reference
In-Depth Information
alleles
{
n1089
deletion
ve20
ok2385
deletion
Mutant
mg152
lin-42c
lin-42b
AAA
lin-42a
PAS domain
AAA
SYQ/LT domains
Figure 6.3 Schematic of the lin-42 locus. The top line indicates the lin-42 genomic locus
with boxes representing exons. The regions encoding the PAS and SYQ/LT domains
conserved in fly and mammalian PER proteins are indicated by hatching and black
boxes, respectively. Untranslated portions of exons are gray. Positions of lesions in
mutant alleles that affect subsets of isoforms are shown above the locus. The first
described alleles (e.g., mg152, n1089, ve20) did not alter the lin-42a transcription unit,
which plays a key role in molting regulation and is deleted in ok2853. A fourth transcrip-
tion unit that lacks the last two exons of lin-42b has been omitted for simplicity.
lin-42a
mutants differ dramatically from wild-type animals during larval
development, exhibiting defects in epidermal cell dynamics and molting at
each larval stage, along with the precocious phenotype in the L3 (
Monsalve
et al., 2011
). Rather than developing in near unison as do populations of
wild-type animals hatched at the same time,
lin-42a
mutants exhibit severe
developmental delays, feed for variable amounts of time prior to an extended
lethargus, and molt asynchronously. Animals at each larval stage can become
stuck during the molt, failing to complete ecdysis, revealing that LIN-42a is
repeatedly required for this process. Moreover, the epidermal seam appears
to be the key site of LIN-42 action for regulating these functions. These
observations indicate that LIN-42a is required for the rapid synchronous
development of wild-type animals and proper execution of molts, leading
to the proposal that the rise and fall of the
lin-42a
isoform directs the cyclical
entry and exit from each molt, thereby pacing this process. That forced tem-
poral mis-expression of
lin-42a
can induce a lethargus-like state and molting
(albeit abnormal) supports this model. This role of
lin-42
in specifying a peri-
odic behavior harkens back again to circadian rhythms, where oscillations in
levels of a similar protein in other organisms link behaviors to the 24-h
clock.
lin-42a
appears to be the elusive factor that integrates successive stage-
specific cell lineage programs and epidermal dynamics with the oscillatory
molting behaviors, pacing this aspect of postembryonic development. If
levels of this LIN-42 isoform are key to the execution and pacing of molts,
