Role of spatiotemporal expression of iodothyronine deiodinase proteins in cerebellar cell organization

Abstract

Thyroid hormones (TH) play a crucial role in various developmental processes in all vertebrates. The expression of a number of thyroid hormone responsive genes is of critical importance in processes like cell maturation and migration. Since these genes are mostly regulated by binding of the receptor-active TH (T(3)) to the thyroid hormone receptor, the availability of this T(3) is indispensable for correct brain lamination. One important way to regulate local TH availability is via the ontogenetic changes in activating and inactivating iodothyronine deiodinases. The current study was set up to investigate the distribution of type I, type II and type III (D1, D2 and D3) iodothyronine deiodinase protein in the chicken cerebellum at two important developmental ages, namely embryonic day 18 when cerebellar cell migration is fully in progress, and 1 day posthatch, when cerebellar maturation is mostly finished. The results show that the deiodinase proteins are divergently expressed in the cerebellar cell population. D1 and D3 are expressed in the granule cells at E18, whereas D2 is found mostly in the molecular layer and the Purkinje cells at that time. One day posthatch, the expression of D1 is limited to the mature granule cells and that of D3 to the Purkinje cells exclusively, whereas D2 remains clearly present in the molecular layer. Comparison of the deiodinase protein distribution with the expression of TH-responsive proteins involved in cell migration (reelin, disabled protein 1 and tenascin-C) allows speculating about the effect of this spatiotemporal distribution pattern on cerebellar cell communicative pathways.