Involvement of thyroid hormones in chicken embryonic brain development.

Thyroid hormones (THs) play an important role in vertebrate brain development by stimulating and coordinating cell proliferation, migration and differentiation. Several TH-responsive genes involved in these processes have been identified, but the information is mainly derived from studies of late brain development, while relatively little is known about the more early stages, prior to the onset of embryonic TH secretion. We have chosen the chick embryo to investigate the role of THs in both late and early brain development. T(4) and T(3) are found in chicken brain from the earliest stages tested (day 4). Indirect clues for the involvement of T(3) in brain development are found in the ontogenetic expression profiles of proteins regulating its bioavailability and action, including TH transporters, deiodinases and TH-receptors. All of them are expressed in whole embryos tested on day 2 of incubation and in developing brain tested from day 4 onwards. Their distribution patterns vary over time and according to the brain area and cell type studied. Hypothyroidism induced during the second half of incubation disturbs cell migration in the cerebellum, providing more direct evidence for the requirement for THs during the later stages of brain development. Direct morphological proof for the requirement for THs during the first half of incubation is still missing, but microarray analysis of telencephalon shows a clearly divergent gene expression profile in hypothyroid embryos. In vivo knockdown of TH transporters and deiodinases in chick embryos cultured ex ovo provides an excellent tool to study the role of THs in early brain development in more detail.