Thyroid hormone regulates TAG-1 expression in the developing rat brain

TAG-1 is a member of the immunoglobulin superfamily of cell adhesion molecu les thought to play important roles in neuronal differentiation and the est ablishment of connectivity during brain development. Because these are proc esses also affected by hypothyroidism, we studied the effects of thyroid ho rmone deprivation and administration on TAG-1 expression in the developing rat brain. By in situ hybridization, immunohistochemistry and Western blott ing we found that TAG-1 RNA and protein levels are upregulated in the hypot hyroid brain. From embryonic day 20 to postnatal day (P) 15, elevated TAG-1 RNA was found in several areas including the cerebral cortex, hippocampus and olfactory bulb. In agreement with this, TAG-1 protein was overexpressed in the major fibre tracts arising from these structures, including the cor pus callosum, anterior and hippocampal commissures and lateral olfactory tr act. A similar overexpression of TAG-1 by hypothyroidism was detected in th e cerebellum, but starting only at P15. In all cases, elevation of TAG-1 RN A and protein expression could be reversed by thyroid hormone treatment. Th ese results show that the deregulation of TAG-1 might contribute to the alt erations caused by the lack of thyroid hormone during brain development.