Biology Reference
In-Depth Information
2012
). Finally, HSD-1 resides in the XXX cells (
Patel et al., 2008
) and pos-
sibly at low levels in the intestine (Antebi, unpublished).
The disparate expression patterns and partial overlap of the biosynthetic
genes are surprising, and suggest that DA production is distributed and
requires transport mechanisms between the tissues. Perhaps the Niemann-
Pick proteins or ABC transporters function to do so. The intriguing question
is, why has the nematode configured the biosynthetic pathway itself to be cell
nonautonomous? Conceivably this could provide a way for each tissue to
communicate to the other and imprint its physiologic state. In this view, each
tissue can cast a vote to regulate developmental progression. Alternately, it
may be a way to concoct tissue-specific ligands at various points in develop-
ment with distinct functions. Understanding the roles of the different tissues
in DA hormone transactions and transport will be an important area to
map out in the future. While classical steroidogenic enzymes of mammals
reside mainly in adrenal and ovary, they are also found in other tissues such
as the skin (
Slominski et al., 2013
). Moreover, vitaminD production requires
specific ring opening steps to be catalyzed in the skin upon exposure to
UV light.
2.5. DA signal amplification enforces reproductive
commitments
Like other life fate choices, the dauer decision entails integrating variable,
complex, and competing environmental cues, as well as diverse physiologic
and metabolic states over time, which must be transformed into a binary all
or none commitment to reproductive growth or arrest. How is this decision
achieved and what are the underlying principles?
Key insights into these questions have come from a study of tissue-specific
daf
-
9
/CYP27A1 regulation and the timing of proreproductive (DA-induced)
versus prodauer (ascaroside-induced) activities.
daf
-
9
::
gfp
is expressed at near
constant levels in the XXX neuroendocrine cells from late embryogenesis into
adulthood, and surprisingly, it is not obviously regulated by inputs from IIS
and TGF-
b
pathways. Evidence indicates, nevertheless, that
daf
-
9
expressed
in these cells helps to prevent dauer formation (
Gerisch & Antebi, 2004;
Mak & Ruvkun, 2004
). By contrast, hypodermal
daf
-
9
is expressed from
mid-L2-L4 around the time of reproductive commitments, and is dramat-
ically regulated by environmental cues as well as dauer signaling pathways,
and thus appears to mediate major regulatory inputs into DA production
(
Gerisch & Antebi, 2004
). Accordingly, hypodermal
daf
-
9
shuts off entirely
under dauer-inducing conditions, and is low but visible under reproductive
