Biology Reference
In-Depth Information
grown on cholesterol deficient media,
C. elegans
larvae exhibit molting
defects, supporting a role for steroid ligands in regulating aspects of this
process (
Yochem, Tuck, Greenwald, & Han, 1999
). In addition, down-
stream components of the fly ecdysone-activated transcriptional cascade
are broadly conserved and several function in molting in the nematode.
The best characterized of these are NHR-23 (similar to fly DHR3 and
mammalian ROR
a
) and NHR-25 (fly
b
FTZ-F1; mammalian SF1), nuclear
receptors whose expression levels cycle with the molts, peaking in the inter-
molt (
Asahina et al., 2000; Gissendanner, Crossgrove, Kraus, Maina, &
Sluder, 2004; Gissendanner & Sluder, 2000; Kostrouchova, Krause,
Kostrouch, & Rall, 1998, 2001
). Whether these conserved receptors
respond to ligand, steroidal or otherwise, has not been established.
The loss of NHR-25 function by mutation or RNAi causes molting
defects and an array of additional phenotypes, including embryonic and larval
lethality and cuticle structural abnormalities (
Asahina et al., 2000; Chen,
Eastburn, & Han, 2004 Gissendanner & Sluder, 2000; Silhankova, Jindra, &
Asahina, 2005
). The molting defect is a manifest as an inability to shed the
old cuticle and results from the loss of NHR-25 function in the epidermis
(
Chen et al., 2004
). The loss of
nhr-23
function causes a similar suite of phe-
notypes, including the inability to shed cuticle at each larval stage
(
Kostrouchova et al., 1998, 2001
). Clarifying the roles of these and potentially
other nuclear receptors in molting will require the identification of their direct
targets, a process now underway (
Kouns et al., 2011
), and the identification of
their ligands (if any). Genome-wide searches have also revealed genes required
to execute molts (
Frand, Russel, & Ruvkun, 2005; Kang et al., 2013
)and
together with more directed studies are beginning to reveal the elements of
a molting pathway. Although some signaling molecules are included, many
of the genes identified act in the mechanics of molting, encoding proteins such
as the collagens that build each cuticle and various peptidases whose functions
include detaching the old cuticle from the epidermis. These types of genes are
critical, providing the nuts and bolts of the molt. But perhaps more fascinating
are the factors that orchestrate molting behaviors with the stage-specific devel-
opmental programs. Periodic regulation of molting is required during larval
stages and must ultimately be terminated to halt the program when the adult
stage is reached. How this regulation is achieved brings us back to the
heterochronic gene pathway.
The failure of retarded heterochronic mutants to limit molting to four
cycles reveals that a terminal output of the timing pathway is to coordinate
the cessation of molting with the transition to adulthood. Here too,
