Biology Reference
In-Depth Information
patterning is achieved. It is perhaps fitting that the first two miRNAs were
discovered here; miRNAs play pivotal roles in the heterochronic gene path-
way, acting as a sequential switches that guide transitions from one larval
stage to the next. Indeed, miRNAs now provide a common thread among
diverse timing pathways in both plant and animal systems. The key miRNA-
target gene associations that guide stage transitions have been identified in
the worm, but much remains to be learned about the functions of the protein
coding targets. The molecular activities of some remain unresolved and the
identities of their direct contacts are largely unknown. In the case of the tran-
scription factors (e.g., LIN-14, HBL-1, DAF-12), direct targets have begun
to be identified, but how they time and organize cell division cycles and
other events remains unclear. Similarly, with LIN-28 we have a glimpse
of one way in which miRNA levels can be timed, but the complete picture
of how miRNA levels are controlled in the pathway promises to be more
complex with additional transcriptional and posttranscriptional inputs.
The first inkling of how molting cycles are paced and aligned with stage-
specific programs has been revealed through the studies of LIN-42; this pro-
tein participates in both functions, controlling molt time and execution
while also acting to specify epidermal lineage patterns. How oscillatory levels
of its various isoforms are programmed and combined to achieve these reg-
ulatory outputs remains to be learned, and the identification of LIN-42's
activity, targets, and interaction partners are prime goals for future studies.
Layered on top of the core heterochronic gene pathway that times larval
development and paces the molts are external inputs that launch and can alter
life history paths. How environmental conditions are transduced to coordi-
nately initiate, and sometimes interrupt and subsequently restart, develop-
mental programs are great problems to pursue. Linking these factors to
environmental cues are key next steps. How does feeding control
mir-235
levels and how do they ultimately modulate the heterochronic pathway?
How does the external environment modulate DAF-12 ligand levels to
allow interruption of larval progression? Ultimately, these combined ave-
nues of study will advance our understanding of the intimate connections
between environmental cues and the mechanisms that temporally pattern
orchestrate developmental transitions.
ACKNOWLEDGMENTS
The authors thank Kate McCulloch for helpful comments on the manuscript. We apologize
to our colleagues whose work could not be cited due to space constraints.
