How thyroid hormone coordinates color

Thyroid hormone boosts the orange color in the skin of developing zebrafish while curtailing the number of black pigmented cells.

Fish with thyroid hormone develop orange pigment cells (left), but if thyroid hormone is lacking they develop too many black pigment cells (right). Image credit: Lauren Saunders (CC BY 4.0)

Hormones control the development of animals from embryos all the way into adulthood. For example, thyroid hormone is needed to transform a tadpole into an adult frog, and it is essential for developing the nervous system and regulating metabolism in countless other adult animals. However, it remains unclear how a single hormone can control such a diverse range of outcomes.

One way to learn more about the effects of thyroid hormone during development is to study zebrafish pigmentation. Pigment cells arise from a group of stem cells in the embryo called the neural crest. Two of these pigment cells respond to thyroid hormone in different ways: it causes orange pigment cells called xanthophores to expand in number, and at the same time limits the number of black pigment cells called melanophores.

To investigate how thyroid hormone effects the numbers of these pigment cells Saunders et al. mapped the active genes of individual cells derived from the neural crest. Further experiments were then performed on the fish themselves based on these gene activity maps. Comparing fish with and without thyroid hormone showed the hormone actually helps both orange and black pigment cells to mature, but in very different ways. For the orange xanthophores, thyroid hormone drives cells already poised to change into their adult form to acquire orange pigments. For the black melanophores, it causes them to mature into their final non-dividing adult state. This results in xanthophores becoming visible just as the number of melanophores is forced to curtail. Saunders et al. also found the receptor for thyroid hormone acts like a brake for both pigment cells, making sure neither cell type matures in the absence of the hormone.

These experiments show how one hormone can independently regulate different cell types as they mature into their adult form. The finding that thyroid hormone limits the growth of melanocytes may explain why people who produce too little thyroid hormone are at greater risk of melanoma – a form of skin cancer that starts in the melanocytes. But more studies are needed to see if thyroid hormone has the same limiting effect on melanocytes in humans.