How thyroid hormones and their inhibitors affect cartilage growth and shape in the frogXenopus laevis

Abstract

Understanding how skeleton changes shape in ontogeny is fundamental to understanding how its shape diversifies in phylogeny. Amphibians pose a special case because their jaw and throat skeleton consists of cartilages that are dramatically reshaped midway through life to support new feeding and breathing styles. Although amphibian metamorphosis is commonly studied by immersing larvae in thyroid hormones (TH), how individual cartilages respond to TH is poorly understood. This study documents the effects of larval stage and TH type (T4 vs. T3), dose and deprivation on the size, shape and morphogenesis of the lower jaw and ceratohyal cartilages in the frog Xenopus laevis. It uses thyroid inhibitors to isolate the effects of each hormone at specific concentrations. It also deconstructs the TH responses into the effects on individual dimensions, and uses measures of percent change to eliminate the effects of body size and growth rate variation. As stage increases, T4 and T3 responses become increasingly similar to each other and to natural remodeling; the differences at low and intermediate stages result largely from abnormal responses to T3. Most notably, the beak-like lower jaw commonly observed at the lowest stage in other studies results largely from arrested growth of cartilage. TH responses are superimposed upon the growth typical for each stage so that cartilages can attain postmetamorphic shapes through dimensional changes that exceed those of natural metamorphosis. Using thyroid inhibitors alters the outcome of TH-induced remodeling, and T4 has almost the same capacity to induce metamorphic shape changes as T3. The results have implications for understanding how the starting shapes of larval elements affect morphogenesis, how chondrocytes behave to change cartilage shape, and how intracellular processing of TH might contribute to interspecific differences in shape change. Also, the data on animal mortality and which stages and doses most closely replicate natural remodeling have practical value for researchers who treat Xenopus tadpoles with TH.

Differences in responsiveness and sensitivity to exogenous disruptors of the thyroid gland in three anuran species

“…Similar to what was reported for Xenopus (Rose & Cahill, ), the premetamorphic tadpoles of D. muelleri exhibit T4‐induced shape changes in the lower jaw decoupled from adjacent tissues. Specifically, the upper jaw articulation remains anterior to produce the observed prognathism (Figure ).…”

“…In Xenopus , the differential responsiveness to exogenous THs for the lower jaw and ceratohyals become increasingly similar to the natural remodelling when the TH exposure is at older stages (Rose & Calhill, ). These authors demonstrated that high doses exposure of early stage tadpoles to TH can induce cartilage elongation and thinning in excess of what occurs naturally in Xenopus species.…”

“…Recent research suggests that the length of the lower jaw and the position of the jaw's articulation in postmetamorphic anurans and some teleost fishes may reflect evolution in the sensitivity and responsiveness of TH in a different lineage. Rose & Cahill (), for example, explored how T4 and triiodothyronine (T3) induce changes in the size, shape, and morphogenesis of the cartilages of lower jaw and ceratohyal in X. laevis . They found abnormal responses in those larvae to T3, and to a lesser degree to T4, resulting in the lower jaw lengthening and projecting beyond the upper jaw, when premetamorphic tadpoles were exposed to high concentration of the hormones.…”

“…Furthermore, like Xenopus , the accelerated remodelling of lower jaw cartilages also alters the normal appearance of the infrarostral elements. Meckelian diverticula are not differentiated in D. muelleri whereas there is a bridge of cartilage between the posterior edges of the infrarostrals in Xenopus (Rose & Calhill, ).…”

“…demonstrated by development acceleration or retardation (Brande‐Lavridsen, Christensen‐Dalsgaard, & Korsgaard, ; Degitz et al, ; Opitz et al, , among others). Some papers have also investigated the biological consequences of endocrine disruption in non‐model species to understand the origin of evolutionary novelties (Bloom et al, ; Jennings & Hanken, ; Laslo, Denver, & Hanken, ; Rose & Cahill, ).…”