Multiple thyroid hormone-induced muscle growth and death programs during metamorphosis in Xenopus laevis

Abstract

Xenopus laevis tadpole tails contain fast muscle fibers oriented in chevrons and two pairs of slow muscle ''cords'' along the length of the tail. When tail resorption is inhibited by a number of different treatments, fast muscle but not the slow cord muscle still is lost, demonstrating that the fast tail muscle is a direct target of the thyroid hormone-induced death program. Expression of a dominant negative form of the thyroid hormone receptor (TRDN␣) was restricted to tadpole muscle by means of a muscle-specific promoter. Even though the transgene protects fast tail muscle from thyroid hormone (TH)-induced death, the tail shortens, and the distal muscle chevrons at the tail tip are degraded. This default pathway for muscle death is probably caused by the action of proteolytic enzymes secreted by neighboring fibroblasts. Nonmuscle tissues that are sensitive to TH, such as the fibroblasts, are not protected by the transgene when it is expressed solely in muscle. If allowed to develop to metamorphosis, these transgenic animals die at the climax of metamorphosis before tail resorption has begun. Their limbs have very little muscle even though the rest of limb morphology is normal. Thus, fast tail muscle and limb muscle have their own cell autonomous death and growth programs, respectively, that are independent of the fate of the other neighboring cell types. In contrast, death of the slow muscle is controlled by the other cell types of the tail.

Apoptosis of tail muscle during amphibian metamorphosis involves a caspase 9-dependent mechanism

“…The first step is activation of the TR by the thyroid hormone signal. This idea is supported by the fact that overexpression of the DNTR represses the TH-induced death in muscle (Schreiber et al, 2001;Das et al, 2002;Nakajima and Yaiota, 2003). The next step is increased production of mRNA encoding the proapoptotic factor Bax (Sachs et al, 1997(Sachs et al, , 2004.…”

“…Recently, it was shown that overexpression of a dominantnegative form of the thyroid hormone receptor (DNTR) has a protective role on numerous TH-sensitive tissues during metamorphosis (Schreiber et al, 2001;Das et al, 2002). Moreover, functional thyroid hormone receptors (TRs) are needed to initiate a cell-autonomous program (suicide mechanism) that induces tail muscle cell death during the initial phase of tail resorption (Nakajima and Yaiota, 2003).…”

“…The activation of the mitochondrial apoptotic pathway in tail muscle cell is represented with the principal actors that have been identified in our study and previous studies. After increases in TH levels (represented here by T 3 ), apoptosis is activated through the thyroid hormone receptor (TR; Schreiber et al, 2001;Das et al, 2002;Nakajima and Yaiota, 2003). By a direct or indirect mechanism, Bax is up-regulated (Sachs et al, 1997(Sachs et al, , 2004) and relocalized at the surface of mitochondria.…”

Dual mechanisms governing muscle cell death in tadpole tail during amphibian metamorphosis

“…A recent communication (Das et al, 2002) reports that fast tail muscle has cell-autonomous death induced by TH. It is shown that fast tail muscle is protected from THinduced death in transgenic tadpoles that express DNTR exclusively in muscle cells.…”

Developmental cell death during Xenopus metamorphosis involves BID cleavage and caspase 2 and 8 activation

“…In Xenopus tadpole, transcript levels of different caspases increase in the regressing tail and remodeling intestine during metamorphosis, supporting a role for caspases in metamorphic cell death (Yaoita and Nakajima, 1997;Nakajima et al, 2000;Rowe et al, 2002;. The activation of caspases-3, -6, -7, and -9 is observed in apoptotic tailderived cells, regressing tail and remodeling dorsal skin (Nakajima et al, 2000;Rowe et al, 2002Rowe et al, , 2005Das, 2002;Schreiber and Brown, 2003;Nakajima and Yaoita, 2003). Moreover, Caspase-3 inhibitors have been shown to impede TH-induced apoptosis of a myoblastic cell line derived from tadpole tail and intestinal cells (Su et al, 1997;Yaoita and Nakajima, 1997).…”