| Thyroid hormone instructs proper neural development, as demonstrated by the devastating neurological outcomes resulting from its absence. However, the mechanism of thyroid hormone action remains poorly understood. Our experiments aim to further clarify thyroid hormone action by focusing on the development of a well-studied model neural tissue, the chick retina. Two thyroid hormone receptors---TRa and TRb2---are expressed in progenitor cells during retinal development and appear to activate just before cell division. Deiodinase 2 and deiodinase 3 are also present, with high levels of Dio2 present in the overlying RPE and Dio3 in progenitors. The different thyroid hormone components function in at least two ways. The first is auto-regulatory, and is characterized by active TRa promoting TRb2 expression, and TRb2 promoting Dio3 expression. Dio3 completes the regulatory loop by inactivating TRa. The second is as a developmental clock, with thyroid hormone receptors timing when a cell begins to express early photoreceptor genes. Using a series of reporter, misexpression, and RNAi techniques, we present a model in which thyroid hormone components regulate their own activity in order to control when---rather than if---a future photoreceptor starts to differentiate. |
