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developmental context; however, one report links
lin-42
activity to a circa-
dian rhythm (
Simonetta, Migliori, Romanowski, & Golombek, 2009
). For
additional consideration of circadian rhythms in
C. elegans
, the reader is
directed to the recent literature (
Hasegawa, Saigusa, & Tamai, 2005;
Migliori, Simonetta, Romanowski, & Golombek, 2011; Olmedo et al.,
2012; Temmerman et al., 2011; van der Linden et al., 2010
).
The cyclic developmental profile of LIN-42 accumulation dramatically
contrasts with the patterns of LIN-14, LIN-28, and HBL-1. Levels of these
proteins are initially high in the L1 epidermis, then stage-specifically
decrease during early larval stages and remain absent (
Fig. 6.2
), yet their
loss-of-function also causes precocious phenotypes (
Abrahante et al.,
2003; Lin et al., 2003; Moss et al., 1997; Ruvkun & Giusto, 1989
). Thus,
lin-42
appears qualitatively different, with an expression pattern suggestive
of multiple or reiterated roles during development. Such a repeated role is
not reflected in the early epidermal lineage patterns of
lin-42
mutants which
appear normal until the L3 molt when an adult-type cuticle appears one
stage early (
Jeon et al., 1999
). However, certain double mutant combina-
tions do reveal epidermal lineage defects prior to the L3 stage, implying ear-
lier redundant role(s) for
lin-42
in controlling these divisions (
Abrahante,
Miller, & Rougvie, 1998; Ren & Zhang, 2010
). But, it is the conspicuous
reiterative pattern of LIN-42 levels, peaking once per larval stage, that is
most evocative, suggesting a possible link to the molting cycle.
Curiously, the first described
lin-42
alleles were only observed to have
defects in the final molt; the first three molts appeared normal despite the
cyclical pattern of
lin-42
expression (
Jeon et al., 1999
). We now know that
early molting defects were hidden by complexities of the
lin-42
locus.
LIN-42 and Period proteins share multiple regions of homology, notably
a PAS domain that mediates protein-protein interactions and smaller
SYQ and LT domains that reside within a C-terminal regulatory region
of Per (
Chang &Reppert, 2003; Tennessen et al., 2006
).
lin-42
encodes four
isoforms, two of which do not overlap. One of these nonoverlapping
isoforms contains the PAS domain (LIN-42c), while the other contains
the SYQ and LT domains (LIN-42a); the remaining two isoforms contain
all of these homology domains (
Fig. 6.3
). The first alleles of
lin-42
left the
SYQ/LT isoform intact, but an important recent study of an allele
(
ok2385
) that completely deletes this isoform (and truncates the long
isoforms) reveals reiterative function(s) for
lin-42
in the molting cycle
(
Monsalve et al., 2011
), and implies that there is some division of labor
among the isoforms.