Thyroid hormone regulates reelin and dab1 expression during brain development

The reelin and dab1 genes are necessary for appropriate neuronal migration and lamination during brain development. Since these processes are controll ed by thyroid hormone, we studied the effect of thyroid hormone deprivation and administration on the expression of reelin and dab1. As shown by North ern analysis, in situ hybridization, and immunohistochemistry studies, hypo thyroid rats expressed decreased levels of reelin RNA and protein during th e perinatal period [embryonic day 18 (E18) and postnatal day 0 (P0)]. The e ffect was evident in Cajal-Retzius cells of cortex layer I, as well as in l ayers V/VI, hippocampus, and granular neurons of the cerebellum. Al later a ges, however, Reelin was more abundant in the cortex, hippocampus, cerebell um, and olfactory bulb of hypothyroid rats (P5), and no differences were de tected at P15. Conversely, Dab1 levels were higher at PO, and lower at P5 i n hypothyroid animals. In line with these results, reelin RNA and protein levels were higher in cu ltured hippocampal, slices from PO control rats compared to those from hypo thyroid animals. Significantly, thyroid-dependent regulation of reelin and dab1 was confirmed in vivo and in vitro by hormone treatment of hypothyroid rats and organotypic cultures, respectively. In both cases, thyroid hormon e led to an increase in reelin expression. Our data suggest that the effect s of thyroid hormone on neuronal migration may be in part mediated through the control of reelin and dab1 expression during brain ontogenesis.