Thyroid hormone shapes craniofacial bones during post-embryonic zebrafish development

Changing the shape of craniofacial bones can profoundly change ecological function, and understanding how developmental conditions sculpt skeletal phenotypes can provide insight into evolutionary adaptations. Thyroid hormone (TH) stimulates metamorphosis and regulates skeletal morphogenesis across vertebrates. To assess the roles of this hormone in sculpting the craniofacial skeleton of a non-metamorphic vertebrate, we tested zebrafish for developmental periods of TH-induced craniofacial shape change. We analyzed shapes of specific bones that function in prey detection, capture and processing. We quantified these elements from late-larval through adult stages under three developmental TH profiles. Under wild-type conditions, each bone progressively grows allometrically into a mature morphology over the course of post-embryonic development. In three of the four bones, TH was required to sculpt an adult shape: hypothyroidism inhibited aspects of shape change, and allowed some components of immature shape to be retained into adulthood. Excess developmental TH stimulated precocious shape change leading to abnormal morphologies in some bones. Skeletal features with functional importance showed high sensitivities to TH, including the transformator process of the tripus, the mandibular symphysis of the lower jaw, the scutiform lamina of the hyomandibula, and the anterior arm of the pharyngeal jaw. In all, we found that TH is necessary for shaping mature morphology of several essential skeletal elements; this requirement is particularly pronounced during larval development. Altered TH titers lead to abnormal morphologies with likely functional consequences, highlighting the potential of TH and downstream pathways as targets for evolutionary change.