Thyroid hormone mediates juvenile and adult craniofacial shape change in zebrafish

Thyroid hormone (TH) is an endocrine factor that stimulates metamorphosis in amphibians and regulates bone morphogenesis across vertebrates. Zebrafish lacking TH show marked changes in skeletal morphology. We hypothesized that physiological TH regulates the shape and ossification of craniofacial elements during the transition from juvenile to adult morphology. To determine how TH shapes the skull, we analyzed microcomputed tomography scans of 175 skulls from juvenile through adult stages of fish reared under a range of TH profiles. To quantify these shape changes, we placed 22 landmarks on reconstructed skulls and analyzed their shapes using 3D geometric morphometrics. We found that hypothyroid fish retained more immature head shapes compared to wild-type counterparts, but that hyperthyroid fish showed no significant difference in overall head shape. While there are significant shape differences at all developmental stages, our data indicate that these shape changes begin early on in development, compound over time, and are most obvious at adult stages. In all, our results suggest that TH regulates populations of skeletogenic cells during craniofacial development and in this way sculpts adult facial morphology.