Regulation of the L1 cell adhesion molecule by thyroid hormone in the developing brain

Thyroid hormone is essential for brain maturation, regulating neuronal diff erentiation and migration, myelination, and synaptogenesis. Mutations in th e cell adhesion molecule L1 cause severe neurological abnormalities in huma ns. We studied the effect of thyroid hormone deprivation and administration on L1 expression. Northern and in situ hybridization studies showed that h ypothyroidism induces a marked increase in L1 mRNA levels in the caudate pu tamen, cerebral cortex, amygdala, and some thalamic nuclei. L1 protein was overexpressed in embryonic and newborn hypothyroid rats in the caudate puta men, internal capsule, habenula, and neocortex. Later in development, an ab normally high L1 expression was found in the cortical and cerebellar white matter, corpus callosum, anterior commissure, thalamocortical projections, and striatal fiber tracts of hypothyroid animals. Thyroid hormone administr ation reversed the upregulation of L1 expression in vivo and in cultured ce lls. Thus, alterations of L1 expression may contribute to the profound abno rmalities caused by hypothyroidism in the developing brain.