Thyroid hormone receptor subtype specificity for hormone-dependent neurogenesis in Xenopus laevis

Thyroid hormone (T3) influences cell proliferation, death and differentiation during development of the central nervous system (CNS). Hormone action is mediated by T3 receptors (TR) of which there are two subtypes, TRα and TRβ. Specific roles for TR subtypes in CNS development are poorly understood. We analyzed involvement of TRα and TRβ in neural cell proliferation during metamorphosis of Xenopus laevis. Cell proliferation in the ventricular/subventricular neurogenic zones of the tadpole brain increased dramatically during metamorphosis. This increase was dependent on T3 until mid-prometamorphosis, after which cell proliferation decreased and became refractory to T3. Using double labeling fluorescent histochemistry with confocal microscopy we found TRα expressed throughout the tadpole brain, with strongest expression in proliferating cells. By contrast, TRβ was expressed predominantly outside of neurogenic zones. To corroborate the histochemical results we transfected living tadpole brain with a Xenopus TRβ promoter-EGFP plasmid and found that most EGFP expressing cells were not dividing. Lastly, treatment with the TRα selective agonist CO23 increased brain cell proliferation; whereas, treatment with the TRβ-selective agonists GC1 or GC24 did not. Our findings support the view that T3 acts to induce cell proliferation in the tadpole brain predominantly, if not exclusively, via TRα.