Thyroid hormone-dependent apoptosis during metamorphosis in Ciona robusta involves both bilaterian-ancestral and vertebrate-derived processes

Chordate metamorphosis is a postembryonic larva-to-juvenile transition triggered by thyroid hormones and their specific receptors (TR). This crucial developmental event shows a wide morphological diversity among different chordate lineages and is characterized by ecological, morphological, metabolic and behavioral changes that can be drastic. One of the most studied models is the amphibian Xenopus, whose tadpole metamorphosis includes apoptosis-induced tail regression dependent on the thyroid hormone pathway. In an evolutionary context, we used the ascidian model, the extant closest group to vertebrates, in which the swimming larva transforms to a sessile filter-feeding juvenile during metamorphosis, to study the role of thyroid hormones in this transformation. The ascidian metamorphosis is also characterized by an apoptosis-driven tail regression as in Xenopus. However, whether this apoptosis-driven process is dependent on the thyroid hormone has not yet been elucidated. In this study, we interfered with thyroid hormone signaling during tail regression of the ascidian Ciona robusta to investigate whether (i) thyroid hormone is involved in the regulation of developmental apoptosis, and (ii) apoptosis leading to tail regression involves its classical molecular pathways. We described specific gene expression landmarks as well as apoptosis dynamics during larva metamorphosis under thyroid hormone exposure and thyroid hormone inhibition treatments. We provide evidence that Ciona robusta metamorphosis involves thyroid hormone-dependent apoptosis, similar to other studied chordates. However, the mode of action of thyroid hormone shows great variation compared to the classically described scheme in chordates, both in thyroid hormone/TR interactions and in the apoptotic pathway.