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Figure 22.4
Beclomethasone-dependent inhibition of fin regeneration is GR dependent.
Zebrafish embryos microinjected at the one-cell stage with GR-directed antisense oligonucleotide
morpholino or control morpholino were amputated at 2dpf and exposed to beclomethasone at 2dpf.
Regeneration was visually assessed at 3dpf.
22.7 THE LARVAL FIN REGENERATION MODEL
The adult fin regeneration model has unique advantages, but its usefulness as a
regenerativemodel is limited by technical barriers such as the length of time necessary
to raise adult fish (2-4 months) and allow for complete fin regeneration (12-14 days)
as well as difficulty achieving genetic manipulation in the fin. It is particularly
challenging to study early signaling events that promote blastema formation because
wound healing must occur prior to microinjection of antisense oligonucleotides that
are commonly used in loss-of-function experiments (Thatcher et al., 2008). Recently,
it was reported that the fin primordia is capable of complete regeneration (2-5 dpf)
similar to the adult zebrafish (Kawakami et al., 2004). Morphologically, even in the
absence of complete cellular differentiation, the larval fin regenerates similarly to the
adult by the development of an apical wound epithelium followed by blastema
formation, which later proliferates and differentiates into the required cell types
(Kawakami et al., 2004). Also, similar to the adult zebrafish, chemical inhibition of
fgfr1 by SU5402, AHR activation by TCDD, and GR activation by beclomethasone
abrogated larval fin regeneration (Poss et al., 2000; Zodrow and Tanguay, 2003;
Mathew et al., 2006, 2007) suggesting that there are similarities at the cellular and
molecular level between adult and larval regeneration. Mainly through marker
analysis, Yoshinari et al. (2009) showed that a number of genes including dlx5a,
msxe, junbl, ilf2, mvp, phlda2, mmp9, hspa9, junb, and smarca4 are expressed in
conserved domains in both the larval and adult models. In support of this, we conducted
a comparative analysis of genes similarly regulated during larval fin and adult fin and
heart regeneration. 64% of the genes that are misregulated during the early stages of
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