Suppression of the Basic Transcription Element-Binding Protein in Brain Neuronal Cultures Inhibits Thyroid Hormone-Induced Neurite Branching

Abstract

Abstract The molecular mechanisms underlying the effect of thyroid hormone (T3) on neurite outgrowth are unknown. We recently identified the small GC-box binding protein BTEB (basic transcription element-binding protein) as a T3-regulated gene in the developing rat brain. BTEB mRNAs are rapidly (by 1 h) up-regulated by T3 in primary rat embryonic neuronal cultures. Antisense oligodeoxynucleotides (ODNs), added to the cultures, reduced by 60% the level of BTEB mRNA. Addition of BTEB antisense ODNs to the cultures, before the onset of neurite polarity, had no effect on neurite elaboration but significantly decreased, in a dose-dependent manner, the effect of T3 on neurite branching. We then examined the effects of antisense ODNs on a thyroid hormone target neuronal population, i.e. the acetylcholinesterase-positive neurons after the onset of neurite polarity. Exposure to BTEB antisense ODNs completely abolished the effects of T3 on neurite branching and on the elaboration of neuritic filopodia-like structures in acetylcholinesterase cells. By contrast, antisense ODNs did not alter the effect of T3 on neurite length. Our results show that titration of BTEB levels by T3 regulates the degree of neurite branching and that the T3-induced neurite elongation and the T3-induced neurite branching are regulated by distinct mechanisms.