Biology Reference
In-Depth Information
growth conditions, strictly correlating with developmental choice.
Perplexingly, under conditions of mild stress, modestly-reduced TGF-
b
or IIS, or limiting DA production, hypodermal
daf
-
9
is massively
upregulated precisely from mid-L2 onwards. It is hypothesized that this
upregulation increases DA production and thus ensures reproductive devel-
opment in the face of mild adversity. By inference, continuous tonic levels
of DA from the XXX are augmented by regulated production in the
hypodermis.
Schaedel and coworkers further addressed organismal fate locking mech-
anisms by examining the antagonistic actions of dauer pheromone and DAs
on the dauer decision during the course of early larval development
(
Schaedel, Gerisch, Antebi, & Sternberg, 2012
). By performing shift exper-
iments they determined that a critical time window (
12-18 h) exists during
the L1/L2 stage in which dauer pheromone exposure was sufficient to drive
dauer formation in wild type. Conversely, coincident exposure of
daf
-
9
null
mutants to DA during this same window could drive reproductive develop-
ment. Through a series of intricate laser ablation studies, they were able to
discern a two step mechanism in which tonic levels of DA emanating from
the XXX cells during the L1 must reach a critical threshold to bypass dauer
(
5-10 nM), which is then amplified within the L2 stage in the hypodermis
to lock in this fate choice, and drive reproductive programs in the somatic
tissues (
Schaedel et al., 2012
). In particular in
daf
-
9
null mutants, which
are unable to amplify this signal, limiting amounts of supplemented DAwere
sufficient to bypass dauer but insufficient to promote normal reproductive
programs of gonadal outgrowth. Higher and sustained DA levels were
required to promote normal reproductive development andmaximal growth
rates. Moreover, the threshold for dauer bypass could be modulated by envi-
ronmental conditions; treatment with ascarosides raised the threshold for
dauer bypass by about 30 nM. Thus, commitment to reproductive develop-
ment is set by plastic thresholds that are modulated by environmental inputs.
Correlatively, titrating DA into
daf
-
9
mutant strains harboring a
pdaf
-
9
::
gfp
transcriptional reporter revealed that the reporter is off in the absence of
DA, on strongly with limiting amounts of DA, but diminished by DA excess.
These dynamics in hypodermal
daf
-
9
expression depend entirely on
daf
-
12
as
well as several other regulators (
Barna et al., 2012; Gerisch & Antebi, 2004;
Mak & Ruvkun, 2004; Monje, Brokate-Llanos, Perez-Jimenez, Fidalgo, &
Munoz, 2011
). These observations imply that both feedforward and feed-
back regulation are critical to ensure binary organismal fate choices. They
also give a striking visible readout of commitments
to reproductive
