Biology Reference
In-Depth Information
can be specifically, yet reversibly, halted in response to environmental cues, including
nutrient availability. Here too, heterochronic genes and miRNAs play key roles. Remark-
ably, developmental arrest can, in some cases, either mask or reveal timing defects asso-
ciated with mutations. In this chapter, we provide an overview of how the C. elegans
heterochronic gene pathway guides developmental transitions during continuous
and interrupted larval development.
1. INTRODUCTION
Developmental transitions can be seen at the level of morphology and
widespread cellular changes, as in insect metamorphosis, or by more subtle
shifts in cell growth and behavior, as when neural cells produce neurons and
then glia. These transitions are fascinating because they imply the existence
of molecular mechanisms that coordinate the behaviors of many cells in
time. We can expect that such mechanisms are not simple, and consist of
many parts with complex interactions and dynamics. To work out how such
transitions are regulated and executed, we need experimental systems that
permit multiple approaches and provide unusual access to the underlying
molecular phenomena.
Two kinds of developmental transitions exemplified by the
Caenorhabditis
elegans
larva are the four stage-to-stage molts on the way to adulthood and an
optional diapause state that can be initiated midway in that course in response
to harsh environmental conditions. The regulation of these two types of
transitions intersects when the normal progress of development is interrupted
and then resumes where it left off. The molecular mechanisms and regulatory
networks underlying these transitions are not simple, but sufficient molecular
details have been elucidated that a few principles have emerged. Persistent
use of classical genetics, combined with one of the first sequenced genomes,
RNA interference, and molecular approaches has revealed a dynamic
network of molecular regulators, switches, and oscillators, that ensure that
cells do the right thing at the right time.
2. A WORM WELL-SUITED TO TIMING STUDIES
C. elegans
is a soil-dwelling nematode, a microscopic worm with an
extremely streamlined anatomy. It emerges from eggshell with exactly
558 cells, and having the necessary nervous system and musculature, it is
competent to forage and feed (see
http://www.wormbook.org/
). What it
