Trimarchi Jeffrey M, Harpavat Sanjiv, Billings Nathan A, Cepko Constance L
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
BMC Dev Biol. 2008 Oct 14;8:101. doi: 10.1186/1471-213X-8-101.
Thyroid hormone (TH) is an important developmental regulator in many tissues, including the retina. TH is activated locally via deiodinase 2 (Dio2), and it is destroyed by deiodinase 3 (Dio3). The TH receptors, TRa and TRb, mediate TH activity through hormone and DNA binding, and interactions with transcription regulators.
In the current work, the expression of these TH components was examined in the chick retina over time. Three waves of expression were characterized and found to be correlated with critical developmental events. The first wave occurred as progenitor cells began to make photoreceptors, the second as some cell types adopted a more mature location and differentiation state, and the third as Müller glia were generated. The cell types expressing the components, as well as the kinetics of expression within the cell cycle, were defined. TRb expression initiated during G2 in progenitor cells, concomitant with NeuroD and Otx2, which are expressed in early photoreceptor cells. TRb was expressed in photoreceptor cells for several days and then was reduced in expression level, as the expression of Crx, a later photoreceptor gene, became more evident. Dio3 was expressed throughout the cell cycle in progenitor cells. TRa was in most, if not all, retinal cells. Dio2 appeared transiently in a ventral (high) to dorsal gradient, likely in a subset of photoreceptor cells.
Multiple TH components were expressed in dynamic patterns in cycling progenitor cells and photoreceptors cells across the developing chick retina. These dynamic patterns suggest that TH is playing several roles in retinal development, both within the cycling progenitor cells and possibly with respect to the timing of differentiation of photoreceptor cells.
甲状腺激素(TH)是包括视网膜在内的许多组织中的重要发育调节因子。TH通过脱碘酶2(Dio2)在局部被激活,并被脱碘酶3(Dio3)破坏。TH受体TRα和TRβ通过激素与DNA结合以及与转录调节因子的相互作用来介导TH的活性。
在当前的研究中,随着时间的推移,对这些TH成分在鸡视网膜中的表达进行了检测。鉴定出了三波表达,并发现它们与关键的发育事件相关。第一波发生在祖细胞开始产生光感受器时,第二波发生在一些细胞类型采用更成熟的位置和分化状态时,第三波发生在米勒胶质细胞产生时。确定了表达这些成分的细胞类型以及细胞周期内的表达动力学。TRβ在祖细胞的G2期开始表达,与早期光感受器细胞中表达的NeuroD和Otx2同时出现。TRβ在光感受器细胞中表达了几天,然后表达水平降低,此时后期光感受器基因Crx的表达变得更加明显。Dio3在祖细胞的整个细胞周期中都有表达。TRα存在于大多数(如果不是全部)视网膜细胞中。Dio2以腹侧(高)到背侧的梯度短暂出现,可能存在于一部分光感受器细胞中。
在发育中的鸡视网膜中,多种TH成分在循环祖细胞和光感受器细胞中以动态模式表达。这些动态模式表明,TH在视网膜发育中发挥着多种作用,既在循环祖细胞内,也可能与光感受器细胞的分化时间有关。