Skull development during anuran metamorphosis: III. Role of thyroid hormone in chondrogenesis.

Metamorphosis of cranial cartilages in anuran amphibians constitutes one of the most dramatic and extensive ontogenetic transformations in vertebrates. We quantitatively exam- ined the role of thyroid hormone (3,3',5-triiodo-L-thyronine; T3) in mediating gross aspects of this morphological repatterning in the skull of the Oriental fire-bellied toad, Bombina orientalis. T3 was administered via plastic (Elvax) micropellets in three treatment dosages (2.5, 0.25, and 0.025 pg) and one control dosage (0 pg) to tadpoles of three G-osner developmental stages -28129, 30131, and 32133; tadpoles were recoved up to 8 d (treatment and control dosages) or 14 d (control dosage) later. Response of larval cartilages to exogenous T3 was dosage dependent but not implant-stage dependent; chondro- genic tissues that participate in metamorphic transformation are competent to respond to T3 well before they normally do. Metamorphic effects of T3 were visible within 2 d; in most treatment groups, the normal metamorphic sequence was two-thirds complete after 8 d. While T3 also induced preco- cious ossification, the normal temporal relation between bone formation and cartilage transformation was dissociated in experimental groups. Morphological integration between cartilage and bone during cranial metamorphosis is at least partly the result of each tissue responding independently to endocrine factors. Among the most remarkable examples of verte- brate organogenesis is the suite of changes that constitute skull development during amphibian, and especially anuran, metamorphosis. In a mat- ter of weeks-days in some species-cranial skele- tal structures are extensively modified coincident with the shift from aquatic to terrestrial habitats: cartilaginous components which predominate in the larval skull are profoundly transformed; bony components which will predominate in the adult make their initial appearance. Moreover, develop- mental events involving both bone and cartilage occur in a precise, orchestrated temporal sequence that achieves a high degree of morphological inte- gration both among components of each skeletal tissue as well as between cartilage and bone. More than a half-century of experimental re- search has extensively documented the primary role of endocrine factors in mediating the diverse morphological and physiological changes that oc- cur during amphibian metamorphosis (Dodd and Dodd, '76; White and Nicholl, '81). Of especial im- portance are thyroid hormones CTH), which, either singly or in concert with other hormones, directly mediate changes in target tissues (Atkinson, '81; Kaltenbach, '68; Kollros, '81). These studies, how- ever, have largely neglected the role of endocrine factors in mediating metamorphic changes in the skeletal system (see references in Hanken and Hall, '88a). This inattention is especially surpris- ing in view of both the dominant role played by hormones, particularly TH, in skeletal develop- ment, growth, and remodeling in other vertebrates (see reviews by Jowsey and Detenbeck, '69; Nijweide et al., '86; Raisz et al., '78; Reddi, '82; Reddi and Sullivan, '80; Silbermann, '831, and the renewed interest in the developmental and regu- latory processes underlying metamorphic transfor- mation in the context of the evolution and devel- opment of morphology and its constraints (Alberch, '87; Alberch and Gale, '86; Lebedkina, '85; Roth and Wake, '85; Wake, '82; Wake and Roth, '85). A recent paper from our laboratory described the prominent role of T3 in cranial ossification during metamorphosis in the Oriental fire-bellied toad, Bombina orientalis (Hanken and Hall, '88a). In the present paper, we reveal the complementary, equally prominent role of T3 in mediating the meta- morphic transformation of cranial cartilages- changes that are in many respects more dramatic and complex than those involving the osteocran- ium. Data constitute both description of the nor- mal metamorphic changes in cartilaginous compo- nents in laboratory-reared specimens and quanti-