Thyroid hormone action in neural development

Effects of thyroid hormone on development of the brain have been documented for over a century. Although in many respects the hypothyroid brain appear s morphologically normal, functional impairments include mental retardation , ataxia and spasticity. Keyed by the discovery of nuclear receptors for th yroid hormone that function as transcription factors, recent work has exami ned the mechanism of thyroid hormone action in brain development. The predi ction that gene expression regulated by thyroid hormone is important for me diating brain development has spurred the search for thyroid hormone-respon sive genes. Here we review some of the identified genes whose expression pa tterns correlate with the functional deficits observed in the hypothyroid b rain. Recently identified thyroid hormone-responsive genes include synaptot agmin-related gene 1 (Srg1), a putative mediator of synaptic structure and/ or activity, and hairless, a transcriptional cofactor that may influence th e expression of other thyroid hormone-responsive genes.