Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Dev Dyn. 2010 Oct;239(10):2700-13. doi: 10.1002/dvdy.22392.
Thyroid hormone and its receptors (TRs) regulate photoreceptor differentiation and visual pigment protein (opsin) expression in the retinas of several vertebrates, including rodents and fish. In some of these animals, opsin expression can arise through switches within differentiated cone photoreceptors. In salmonid fishes, single cones express ultraviolet (SWS1) opsin during embryonic development and switch to blue (SWS2) opsin as the fishes grow. It is unknown whether thyroid hormone regulates opsin expression during early cone differentiation and acts through TRs to induce opsin switches in differentiated cones of the salmonid retina. Using in situ hybridization, we characterized the spatiotemporal dynamics of opsin expression and switching in embryos treated with exogenous thyroid hormone or propylthiouracil (PTU), a pharmacological inhibitor of thyroid hormone synthesis. We combined immunohistochemistry with in situ hybridization to map TRα expression with respect to cones undergoing the opsin switch in older juvenile fish. Thyroid hormone accelerated opsin expression in differentiating cones and induced the opsin switch in differentiated single cones, whereas PTU repressed the opsin switch. TRα was not detected in differentiating photoreceptors as opsin expression initiated, but was later expressed in differentiated single cones before the onset of the opsin switch. TRα expression exhibited a dynamic dorsoventral distribution that paralleled the progression of the opsin switch. Together, our results show that thyroid hormone is required for opsin switching in the retina of salmonid fishes and suggest that TRα may be involved in regulating this phenomenon.
甲状腺激素及其受体(TRs)调节包括啮齿动物和鱼类在内的几种脊椎动物的光感受器分化和视觉色素蛋白(opsin)表达。在这些动物中,一些 opsin 的表达可以通过分化的视锥细胞内的开关来实现。在鲑鱼目中,单视锥细胞在胚胎发育过程中表达紫外线(SWS1)opsin,并在鱼类生长过程中转变为蓝色(SWS2)opsin。目前尚不清楚甲状腺激素是否在早期视锥细胞分化过程中调节 opsin 的表达,并通过 TRs 诱导鲑鱼视网膜分化的视锥细胞中的 opsin 开关。通过原位杂交,我们研究了外源性甲状腺激素或丙硫氧嘧啶(PTU)处理的胚胎中 opsin 表达和转换的时空动态,PTU 是甲状腺激素合成的药理学抑制剂。我们将免疫组织化学与原位杂交相结合,以在接受甲状腺激素或丙硫氧嘧啶(PTU)处理的幼年鲑鱼中,根据正在进行 opsin 转换的视锥细胞来绘制 TRα 表达图谱。甲状腺激素加速了分化中的视锥细胞的 opsin 表达,并诱导分化的单视锥细胞发生 opsin 转换,而 PTU 则抑制了 opsin 转换。在 opsin 表达开始时,未在分化的光感受器中检测到 TRα,但在 opsin 转换开始之前,它在分化的单视锥细胞中表达。TRα 的表达表现出与 opsin 转换进展平行的动态背腹分布。总的来说,我们的结果表明甲状腺激素是鲑鱼视网膜中 opsin 转换所必需的,并且表明 TRα 可能参与调节这一现象。