Biology Reference
In-Depth Information
lin-29
, which is required for terminal differentiation of epidermal cells,
encodes a transcription factor that can directly regulate terminal differenti-
ation genes (
Rougvie & Ambros, 1995
).
The genes directing these three phases form the core heterochronic path-
way. In general, these genes have highly penetrant and unambiguous phe-
notypes when mutated. Other factors governing developmental timing in
C. elegans
are characterized by how they integrate into this core pathway.
Still, there is quite a bit missing from this picture, not least of which is
how the boundaries between the larval stages fit in.
7. DEVELOPMENTAL TRANSITIONS: THE MOLTS
The heterochronic pathway and molting control must be intimately
linked. The very boundaries of the stages are the molts, and the heterochronic
pathway confers temporal identity on cells during the intermolt period.
Furthermore, precocious mutants like
lin-14
and
lin-28
cease the molting
cycle at least one stage too soon, while retarded mutants like
lin-4
and
lin-29
continue molting indefinitely. One expects that the mechanisms
coordinating the animal-wide process of molting influence the rise and fall
of heterochronic factors that determine the stage-specific cell fates.
Molting is a defining feature of the Ecdysozoa clade of which both
C. elegans
and
Drosophila
are members (
Aguinaldo et al., 1997
). The mech-
anisms
that guide molting are best understood in flies where pulses of the
cholesterol-derived steroid hormone 20-hydroxyecdysone (20-E) impose
temporal transitions during the life cycle, timing molting and metamorpho-
sis, by acting through a nuclear receptor heterodimer composed of the ecdy-
sone receptor (EcR) and its partner ultraspiracle (USP) (
Koelle et al., 1991;
Yao et al., 1993; Yao, Segraves, Oro, McKeown, & Evans, 1992
). The sig-
nals generated by these periodic interactions induce expression of additional
nuclear receptors (DHR3,
b
Ftz-F1, and others) in a precise sequence that
temporally patterns the molts and metamorphosis in a coordinated fashion
throughout the organism.
C. elegans
neither synthesizes nor appears to respond to ecdysteroids, and
it lacks EcR and USP orthologs (
Chitwood & Feldlaufer, 1990; Sluder,
Mathews, Hough, Yin, & Maina, 1999
), indicating that molting in this
organism is launched by a different trigger. Nevertheless, some aspects of
molting control appear to be more universal, with steroid mediated
responses providing a unifying theme. The worm lacks cholesterol biosyn-
thesis enzymes and instead depends upon dietary intake of this steroid. When
