Biology Reference
In-Depth Information
Two genes were identified as possible candidates for neural-specific
development, Notch and Otx2 (
Das et al., 2006
). Notch activation by TH
occurs in the same replicating cells that line the brain and spinal cord ventricle,
and the homeobox protein Otx2 has been implicated in mouse brain devel-
opment. Because brain remodeling requires 1-2 weeks, 48 h of TH treat-
mentmay not be the appropriate time point to capture altered expression
of genes regulating adult brain differentiation and thus more studies are needed
to identify such genes.
2.3. Hind limb
The first response to TH in the limb is cell proliferation, which begins
within 1-2 days after TH treatment (
Brown & Cai, 2007
). Subsequently,
limb differentiation also occurs where muscle, nerves, and skeletal elements
form coordinately. The predominant TH-induced morphological change in
the limb is elongation of the elements, as limb patterning can occur in the
absence of TH. TH-induced gene expression profiles were carried out on
hind limbs of premetamorphic tadpoles treated with 100 nM TH for 14,
24, 48 h (
Das et al., 2006
). Microarray studies targeting the beginning of
the gene regulation cascade in the hind limb were compared to initial steps
of the cascade in tail and brain to gain insight into how different tissues can
respond differently to TH.
As in the brain, the hind limb program during the first 48 h of TH treat-
ment reflects the intense proliferation that occurs then. The TH-induced
limb program shares many genes and virtually all functional categories with
the early brain program (
Fig. 12.3
). Specifically, more than 92% of 955 genes
that are upregulated in the brain are also upregulated in the limb after 48 h of
TH treatment. Similarly, more than 88% of 199 genes that are down-
regulated in brain are also downregulated in the hind limb. Genes involved
in every step of the cell cycle are TH-regulated and the two programs are
remarkably similar containing many cell cycle-related genes. Also, there is
high representation of enriched gene products that reside in the nucleolus,
which are related to this increase in translation-related proteins. Half of the
genes in the array that encode protein-folding proteins are upregulated in
the hind limb including chaperone proteins. Many of the components that
are involved in the ubiquitination and proteosome pathways are also
upregulated, especially in the limb program.
In every functional category, there are more genes upregulated in the
hind limb than in the brain and the extent that they are differentially
