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TH-induced development goes toward a developmental state not capable of
regeneration. To look for genes potentially involved in this process, micro-
array was done using hindbrain, the source of regenerating axons. The au-
thors focused on genes upregulated by spinal cord injury in the regeneration
permissive state (MMI treated) and found 72 annotated genes, including
transcription factors, membrane proteins, cell-cell and intracellular signal-
ing, and transcriptional coregulators. The five most regulated genes were
SOCS2, XER81, neurotensin, MORC3, and a protein associated with
RNA polymerase. All but the last of this list have known functions in pro-
moting neural development, survival, and neurite outgrowth. The larval
state appears to be important for regeneration, and characterizing precisely
the larval state and which specific genes involved in regeneration will require
functional studies on candidate genes.
5. SUMMARY AND CONCLUSIONS
Knowledge of how TH can induce wildly divergent responses among
tissues during frog metamorphosis will include identification of the compo-
nent genes of TH-induced tissue-specific gene regulation cascades. Micro-
array analyses have contributed most significantly to this effort and have also
revealed aspects of TH-induced metamorphosis unanticipated by previous
morphological and physiological studies. As expected, each organ has
unique TH-regulated genes concordant with its distinct role in the organ-
ism, for example, larval and adult keratins in the skin, proteins associated
with nutrient absorption in the intestine. On the other hand, some tissues,
such as brain, limb, and intestine, have a large set of commonly regulated
genes despite having distinct morphological outcomes. These common
genes are comprised of cell cycle genes and consistent with cell proliferation
as a component of their metamorphic remodeling. In this respect, the cor-
relation between expected functions of genes in cell biology and histological
observation were consistent, thereby matching known morphological
events with molecular signatures. Similarly, the tail and intestine had over-
lapping sets of genes, including decreased metabolism and electron transport
chain proteins and increased extracellular proteases, consistent with tail re-
gression and apoptosis of larval intestinal epithelium. Visualization of these
comparisons among tissues reveals that cellular responses to TH induction,
such as mitochondrial and cell cycle regulation, are much more divergent
among tissues
than changes
in transcription and signal
transduction
( Fig. 12.3 ).
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