Biology Reference
In-Depth Information
These studies have focused on the skin and brain, the former because it is a
peripheral target tissue of TH and much is known about anatomical changes
that occur during metamorphosis (
Fahrmann, 1971a, 1971b, 1971c; Fox,
1983; Page, Monaghan, Walker, & Voss, 2009
). The brain has also been
targeted because it is where HPT and HPI axes are centrally regulated.
We review three important findings from these studies.
T4 precisely activates metamorphic transcriptional programs in a concentration
-
dependent manner
.
Page et al. (2008)
varied T4 concentration by an order
of magnitude and examined transcriptional patterns in
A. mexicanum
skin
after 0, 2, 12, and 28 days of T4 treatment. Individuals exposed to 50 nM
T4 initiated metamorphosis approximately 1 week prior to those in
5 nM, however, the sequence of transcriptional and morphological changes
during metamorphosis, and the length of the metamorphic period did not
differ (
Fig. 8.4
A). Over 1000 genes were identified as differently expressed
in both treatments, showing the same directional trends, but the patterns
were temporally shifted by T4 concentration. The study showed that the
timing of metamorphic onset is T4 concentration dependent, and surpris-
ingly, high T4 concentration did not disassociate subsequent transcriptional
programs. It remains to be determined if the T4 concentration effect
in
A. mexicanum
is manifested at the level of target cells, the HPT axis, or
possibly both (
Rosenkilde & Ussing, 1996
).
Patterns of gene expression are complex
,
reflecting tissue remodeling
,
changes in
cellular metabolism
,
and loss and gain of larval and adult cell types.
One of the
advantages in working with
A. mexicanum
is that they present a natural, hypo-
thyroid condition throughout life (
Huggins et al., 2012
). Thus, transcriptional
programs can be activated precisely at juvenile or adult stages of the life cycle.
When T4 is administered, thousands of genes show significant changes in tran-
script abundance. In a very general sense, these genes show four temporal gene
expression patterns: they increase or decrease in abundance, or they transiently
increase or decrease during metamorphosis (
Fig. 8.4
B). Linear, quadratic, and
piece-wise regression models have been used to identify groups of genes that
similarly increase or decrease in abundance as a function of days of T4 treat-
ment. The earliest gene expression changes precede tissue-remodeling events
and are associated with cells that are specific to larvae or cells that differentiate
to form adult tissues. For example, after 2 days of T4 treatment, genes that
are specifically expressed in apical and Leydig cells of the larval skin show
decreases in transcript abundances (
Page et al., 2007, 2008, 2009
). At this
time, apical and Leydig cell numbers are normal for larval skin and there is
no histological evidence of remodeling. However, after 12 days of T4
