Biology Reference
In-Depth Information
then several questions need answers. How are its expression dynamics con-
trolled? What are the targets of LIN-42a activity and do they include
let-7
family miRNAs? And what are contributions of the other isoforms? These
issues are presently being intensely studied. Transcription factors required
for cyclical
lin-42
expression have not been reported, but nuclear receptors,
of which there are many in
C. elegans
, are good candidates and could allow
for endocrine control of the process. There is also potential for regulatory
interactions among the LIN-42 isoforms. Over-expression of
lin-42a
can
rescue the heterochronic defects of all tested mutations in the locus,
suggesting that its high dosage can compensate for lack of the other isoforms
(
Tennessen et al., 2006
), perhaps overcoming a missing regulatory or intra-
cellular targeting function. Also curious is the observation that over-
expression of the
lin-42c
PAS-domain isoform can antagonize the
lin-42a
mutant phenotype (
Monsalve et al., 2011
). Although the biochemical roles
of each isoform await identification, analogy to Per, together with its nuclear
localization, suggests LIN-42 is likely to regulate transcription of down-
stream genes that control epidermal cell behaviors and integrate them
temporally with the molts.
In addition to programming molts,
lin-42
exerts another important influ-
ence as it charts an efficient path to reproductive maturity—it mediates
organismal responses to environmental conditions. In this capacity,
lin-42
participates in the decision of whether to interrupt the molting cycles of con-
tinuous development to enable dauer formation. Here, LIN-42 acts to antag-
onize the ligand-free form of the nuclear receptor DAF-12 (
Tennessen,
Opperman, & Rougvie, 2010
).
9. REVERSIBLE INTERRUPTION OF DEVELOPMENTAL
PROGRESSION: DAF-12
The DAF-12 nuclear receptor plays a unique role in nematode life his-
tory regulation by controlling the choice between developing rapidly
through each larval stage to reach reproductive maturity versus executing
a contingency plan, dauer larva formation, in response to unfavorable
growth conditions (
Antebi, Culotti, & Hedgecock, 1998; Antebi, Yeh,
Tait, Hedgecock, & Riddle, 2000
). The ability to interrupt reproductive
development for dauer formation intertwines many regulatory pathways.
Environmental signals are received and conveyed throughout the animal
to interrupt the molting cycle and halt one set of stage-specific programs
in order to implement another, while maintaining the ability to coordinately
