Endocrine regulation of multichromatic color vision.

Vertebrate color vision requires spectrally selective opsin-based pigments, expressed in distinct cone photoreceptor populations. In primates and in fish, spectrally divergent opsin genes may reside in head-to-tail tandem arrays. Mechanisms underlying differential expression from such arrays have not been fully elucidated. Regulation of human red () vs. green () opsins is considered a stochastic event, whereby upstream enhancers associate randomly with promoters of the proximal or distal gene, and one of these associations becomes permanent. We demonstrate that, distinct from this stochastic model, the endocrine signal thyroid hormone (TH) regulates differential expression of the orthologous zebrafish / array, and of the tandemly quadruplicated /// array. TH treatment caused dramatic, dose-dependent increases in abundance of , the proximal member of the array, and reduced Fluorescent reporters permitted direct visualization of individual cones switching expression from to Athyroidism increased and reduced , except within a small ventral domain of that was likely sustained by retinoic acid signaling. Changes in abundance and distribution in athyroid zebrafish were rescued by TH, demonstrating plasticity of cone phenotype in response to this signal. TH manipulations also regulated the array, with athyroidism reducing abundance of distal members. Interestingly, the opsins encoded by the proximal gene and distal genes are sensitive to longer wavelengths than other members of their respective arrays; therefore, endogenous TH acts upon each opsin array to shift overall spectral sensitivity toward longer wavelengths, underlying coordinated changes in visual system function during development and growth.