Unliganded Thyroid Hormone Receptor Regulates Metamorphic Timing via the Recruitment of Histone Deacetylase Complexes - Current Topics in Developmental Biology - page 284

Stage 52 54 56 58 60 61 62 63 64 66

EP
CT
MU

L

Intestinal
remodeling

Limb morphogenesis

Tail resorption
Figure 10.5 Temporal regulation of tissue specific metamorphosis. The developmental
stages are based on Nieuwkoop and Faber (1956) . The tails at stages 62 - 66 are drawn to
the same scale to show the resorption (no tail at stage 66), while the tadpoles, intestinal
cross-sections and hindlimbs at different stages are drawn in arbitrary sizes to highlight
the morphological differences. Tadpole small intestine has a single epithelial fold, where
connective tissue (CT) is abundant, while a frog has a multiply folded intestinal epithe-
lium (EP), with elaborate connective tissue and muscle (MU). Dots, proliferating adult
intestinal epithelial cells; open circles, apoptotic primary or larval intestinal epithelial
cells; L, intestinal lumen.

( Fig. 10.5 ). A number of factors appear to contribute to this temporal regula-
tion of organ-specific metamorphosis. These factors affect two aspects of TH
signaling: TR-RXR heterodimer levels and availability of intracellular TH.
Expression analyses of TR and RXR have shown that the mRNAs
for TR a ,TR b , and RXRs are highly expressed during amphibian
metamorphosis ( Davey, Schneider, & Galton, 1994; Eliceiri & Brown,
1994; Fairclough & Tata, 1997; Helbing, Gergely, & Atkinson, 1992;
Kawahara, Baker, & Tata, 1991; Schneider & Galton, 1991; Wang &
Brown, 1993; Wang, Matsuda, & Shi, 2008; Wong & Shi, 1995;
Yaoita & Brown, 1990 ). Importantly, the expression of TR and RXR genes
in individual organs during Xenopus metamorphosis strongly correlates with
the temporal regulation of organ-specific transformations ( Eliceiri & Brown,
1994; Wang & Brown, 1993; Wang et al., 2008; Wong & Shi, 1995;
Yaoita & Brown, 1990 ). In general, TR and RXR genes are coordinately
regulated during metamorphosis and their expression is high in a given
organ when metamorphosis takes place and low before or after meta-
morphosis ( Table 10.1 ). Thus, the mRNA levels for these receptor genes
(except for TR b genes) are high in the hindlimb around stages 54-56 when
hindlimb morphogenesis, for example, digit formation, takes place ( Wang &