Thyroid hormone (TH) signaling plays an important role in the regulation of long-wavelength vision in vertebrates. In the retina, thyroid hormone receptor β (thrb) is required for expression of long-wavelength-sensitive opsin (lws) in red cone photoreceptors, while in retinal pigment epithelium (RPE), TH regulates expression of a cytochrome P450 enzyme, cyp27c1, that converts vitamin A₁ into vitamin A₂ to produce a red-shifted chromophore. To better understand how TH controls these processes, we analyzed the phenotype of zebrafish with mutations in the three known TH nuclear receptor transcription factors (thraa, thrab, and thrb). We found that no single TH nuclear receptor is required for TH-mediated induction of cyp27c1 but that deletion of all three (thraa^−/−;thrab^−/−;thrb^−/−) completely abrogates its induction and the resulting conversion of A₁- to A₂-based retinoids. In the retina, loss of thrb resulted in an absence of red cones at both larval and adult stages without disruption of the underlying cone mosaic. RNA-sequencing analysis revealed significant down-regulation of only five genes in adult thrb^−/− retina, of which three (lws1, lws2, and miR-726) occur in a single syntenic cluster. In the thrb^−/− retina, retinal progenitors destined to become red cones were transfated into ultraviolet (UV) cones and horizontal cells. Taken together, our findings demonstrate cooperative regulation of cyp27c1 by TH receptors and a requirement for thrb in red cone fate determination. Thus, TH signaling coordinately regulates both spectral sensitivity and sensory plasticity.

甲状腺激素 (TH) 信号在脊椎动物长波视觉的调节中起重要作用。在视网膜中，红锥光感受器中长波敏感视蛋白 ( lws ) 的表达需要甲状腺激素受体 β ( thrb ) ，而在视网膜色素上皮 (RPE) 中，TH 调节细胞色素 P450 酶cyp27c1 的表达，将维生素 A ₁转化为维生素 A ₂以产生红移发色团。为了更好地了解 TH 如何控制这些过程，我们分析了三种已知 TH 核受体转录因子（thraa、thrab、和 thrb）。我们发现 TH 介导的cyp27c1诱导不需要单个 TH 核受体，但删除所有三个（thraa ^-/- ;thrab ^-/- ;thrb ^-/-）完全消除了它的诱导和由此产生的 A _{1 的}转化- 以A ₂为基础的类视色素。在视网膜中，thrb 的损失导致在幼虫和成虫阶段都没有红锥，而没有破坏下面的锥镶嵌。RNA 测序分析显示成人thrb ^-/-视网膜中只有五个基因显着下调，其中三个（lws1、lws2和miR-726 ) 出现在单个同线簇中。在thrb ^-/-视网膜中，注定要变成红色视锥细胞的视网膜祖细胞被转化为紫外线 (UV) 视锥细胞和水平细胞。综上所述，我们的研究结果表明TH 受体对cyp27c1的协同调节以及红锥命运决定中对thrb的要求。因此，TH 信号协同调节光谱敏感性和感官可塑性。