Orphan nuclear receptors and mammalian development

一个器官或组织的发育通常取决于一系列基因连续激活的遗传控制等级。这些基因的活性指导细胞分化事件，将一个很大程度上未特化的细胞团转变为成熟的功能器官。编码转录因子的基因通常在这些发育途径中起关键作用。核受体是配体调节的转录因子，对激素或其他配体作出反应。孤儿受体是核受体的一个特殊亚类，缺乏已知的生理配体，可能具有组成性转录功能。类视黄醇相关孤儿核受体b （RORb）由RORb基因编码，在大脑和视网膜中特异性表达。视网膜中的表达模式暗示了神经发生和光感受器分化的后续阶段的功能。然而，Rorb在视网膜中的功能仍不明确。因此，对Rorb基因的研究提供了一个机会来阐明一个孤儿核受体在一个确定的发育系统，视网膜中的新功能。进展:

The development of an organ or tissue often depends upon a genetic hierarchy of control involving the successive activation of a series of genes. The activity of these genes directs the cellular differentiation events that change a largely un-specialized cell mass into a mature and functioning organ. Genes encoding transcription factors are often critical in such developmental pathways. Nuclear receptors are ligand-regulated transcription factors that respond to hormones or other ligands. Orphan receptors are a special sub-class of nuclear receptors that lack known physiological ligands and may have constitutive transcriptional functions. The retinoid-related orphan nuclear receptor b (RORb), encoded by the Rorb gene, is specifically expressed in the brain and retina. The expression pattern in retina is suggestive of functions in neurogenesis and in the subsequent stages of differentiation of photoreceptors. However, the functions of Rorb in retina remain poorly defined. The study of the Rorb gene therefore offers the opportunity to elucidate novel functions for an orphan nuclear receptor in a defined developmental system, the retina. Progress: 1. The role of the Rorb gene in cone development. In dichromatic mammals, cones express opsin photopigments that are sensitive to short (S, blue) or medium-longer (M, green) wavelengths of light. The mechanisms that differentially regulate M and S opsin expression are critical for color vision but are incompletely understood. Our analysis has indicated that the Rorb gene induces the S opsin gene in cone development. The results suggest that the S opsin gene is directly regulated by binding of the RORb protein in cone maturation. 2. Ongoing studies suggest that RORb is also involved in the rod developmental pathway (collaboration with Dr Anand Swaroop, NEI). Preliminary data indicate that these functions are distinct from those in cones. The data suggest that RORb is multi-functional, having independent roles in different retinal cell populations.