Huang, L.; Bartel, R.C.*; Denver, R.J.: Thyroid Hormone Promotes Cell Proliferation, Migration and Differentiation in the Xenopus laevis Tadpole Brain.
The essential role of thyroid hormone (T3) in amphibian metamorphosis has been understood for some time. However, the mechanisms by which it causes pleiotropic effects remain unknown. Our group seeks to characterize the molecular action of thyroid hormone in the larval brain. In this study, we investigated the effects of thyroid hormone on cell proliferation, migration and differentiation during metamorphosis of the Xenopus tadpole. For cell proliferation studies, premetamorphic tadpoles were treated with 500 nM Bromo deoxyuridine (Brdu) with or without 50 nM T3 for 24, 48, 72 and 96 hours. Samples were then processed for Brdu immuno-histochemistry (IHC) or in situ hybridization for the thyroid hormone receptor (TR) ALPHA and BETA isoforms. Our preliminary IHC and in situ analyses demonstrate that T3 dramatically increases cell birth within the periventricular zone and that both TR-ALPHA and TR-BETA messages are elevated in this region. We are currently attempting to colocalize these signals with Brdu immunoreactivity. In our migration studies, animals were pulsed in 500 nM Brdu, cleared for 24 hours and then treated with or without 50 nM T3 for 24, 48, 72 or 96 hours. Brdu immunoreactivity is weaker and more dispersed throughout the brains of T3 treated animals. Furthermore, most of the Brdu immunoreactive cells in T3 treated brains have elongated nuclei, which is characteristic of migration. Together these data suggest that T3 treatment shortens cell cycle and accelerates cell migration away from the periventricular zone