Thyroid Hormone Receptor Alpha Is Required for Thyroid Hormone-Dependent Neural Cell Proliferation During Tadpole Metamorphosis

Thyroid hormone (T3) plays key roles in nervous system development in vertebrates, controlling diverse processes such as neurogenesis, cell migration, apoptosis, differentiation and maturation. In anuran amphibians, the hormone exerts its actions on the tadpole brain during metamorphosis, a developmental period entirely dependent on T3. Thyroid hormone regulates gene transcription by binding to two nuclear receptors, TRα and TRβ. Our previous findings using pharmacological and other approaches supported that TRα plays a pivotal role in mediating T3 actions on neural cell proliferation in Xenopus tadpole brain. Here we used X. tropicalis tadpoles with an inactivating mutation in the gene that encodes TRα to investigate roles for TRα in mitosis and gene regulation in tadpole brain. Gross morphological analysis showed that mutant tadpoles had proportionally smaller brains, corrected for body size, compared with wildtype, both during prometamorphosis and at the completion of metamorphosis. This was reflected in a large reduction in phosphorylated histone 3 (pH3; a mitosis marker) immunoreactive (ir) nuclei in prometamorphic tadpole brain, when T3-dependent cell proliferation is maximal. Treatment of wild type premetamorphic tadpoles with T3 for 48 hr induced gross morphological changes in the brain, and strongly increased pH3-ir, but had no effect in mutant tadpoles. Thyroid hormone induction of the direct TR target genes thrb, klf9 and thibz was dysregulated in mutant tadpo...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research