Biology Reference
In-Depth Information
development. Critical tests of this model await measuring DA production in
each tissue during the course of development. Conceivably analogous ampli-
fication mechanisms are deployed to drive maturational processes in insects
and mammals.
3. DAF-12 REGULATES DEVELOPMENTAL TIMING
3.1. Heterochronic genes
In the course of animal development, cells throughout the body acquire
both temporal and positional identities. As
C
.
elegans
develops from embryo
through four larval stages L1-L4 and on to adult, each stage elaborates a
characteristic array of cellular programs of division, differentiation, morpho-
genesis/migration, and death. In particular, certain tissues are explicitly tem-
porally patterned, including division patterns of epidermal seam cells and
intestinal cells, or morphogenesis of the vulva and gonad during larval devel-
opment. Temporal selector genes called the heterochronic loci dictate the
stage-specific temporal patterning of cell fate. Their mutation can lead to
either precocious or retarded execution of cellular temporal patterns, which
in some tissues manifests as a deletion or repetition of stage-specific pro-
grams. They often work in a stage- and tissue-specific manner and cooperate
in a regulatory hierarchy, called the heterochronic circuit, which controls
the proper succession of developmental events.
Many of the heterochronic loci encode conserved regulators including the
very first discovered microRNAs,
lin
-
4
and
let
-
7
, as well as genes involved in
their activity, biogenesis, and maturation (
Lee, Feinbaum, & Ambros, 1993;
Reinhart et al., 2000
). For example, the conserved
lin
-
28
gene encodes an
RNA-binding protein that inhibits the maturation of
let
-
7
microRNA
(
Moss, Lee, & Ambros, 1997; Rybak et al., 2008; Viswanathan, Daley, &
Gregory, 2008
). Extraordinarily, the mammalian homologs of LIN-28 regu-
late the timing of puberty (
He et al., 2009; Ong et al., 2009; Sulem et al., 2009;
Zhu et al., 2010
). Moreover, mammalian LIN28 works as a pluripotency fac-
tor essentially collaborating with other such factors to reprogram terminally
differentiated cells to a primordial temporal fate (
Yu et al., 2007
). These
and other studies highlight the original and groundbreaking work first uncov-
ered by this tiny corner of
C
.
elegans
biology.
3.2. The microRNA paradigm
An emergent paradigm for temporal control of development is that micro-
RNAs work in succession as switches that catalyze transitions from earlier
