Notch-mediated thyroid hormone regulation of skin development in the zebrafish caudal fin

Thyroid hormone (TH) is a systemic regulator of vertebrate development, yet its role in the maturation of the stratified skin remains poorly defined. Using the skin at the edge of the zebrafish caudal fin, we defined the trajectory of epidermal maturation during the transition from juvenile to adult. We found the peripheral edge (PE) of the fin exhibits positive allometric expansion that is dependent on TH: in thyroid-ablated, hypothyroid backgrounds, the growth of the PE is limited. We showed that TH drives normal PE growth by stimulating both cell proliferation and hypertrophy. Further, we demonstrated that TH acts upstream of the Notch pathway to regulate growth of the PE. While TH signaling machinery is broadly expressed throughout the fin, Notch pathway activation is localized and highly enriched in the PE. Repressing Notch activity prevented PE expansion, while upregulating Notch in a hypothyroid background was sufficient to increase hypertrophy and partially rescue PE expansion. By identifying Notch as a region-specific effector of TH-driven hypertrophy, our findings show a mechanism by which systemic endocrine signals are translated into local tissue morphogenesis.