Basic transcription element-binding protein (BTEB) is a thyroid hormone-regulated gene in the developing central nervous system - Evidence for a rolein neurite outgrowth

Thyroid hormone (3,5,3'-triiodothyronine; T-3) is essential for normal deve lopment of the vertebrate brain, influencing diverse processes such as neur onal migration, myelin formation, axonal maturation, and dendritic outgrowt h. We have identified basic transcription element-binding protein (BTEB), a small GC box-binding protein, as a T-3-regulated gene in developing rat br ain. BTEB mRNA levels in cerebral cortex exhibit developmental regulation a nd thyroid hormone dependence. T-3 regulation of BTEB mRNA is neural cell s pecific, being up-regulated in primary cultures of embryonic neurons (E16) and in neonatal astrocytes (P2), but not in neonatal oligodendrocytes (P2), T-3 rapidly up-regulated BTEB mRNA in neuro-2a cells engineered to express thyroid hormone receptor (TR) pi but not in cells expressing TR alpha 1, s uggesting that the regulation of this gene is specific to the TR beta 1 iso form, Several lines of evidence support a transcriptional action of T-3 on BTEB gene expression. Overexpression of BTEB in Neuro-2a cells dramatically increased the number and length of neurites in a dose-dependent manner sug gesting a role for this transcription factor in neuronal process formation. However, other T-3-dependent changes were not altered; i.e. overexpression of BTEB had no effect on the rate of cell proliferation nor on the express ion of acetylcholinesterase activity.