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

Thyroid hormone (3,5,3'-triiodothyronine; T-3) is essential for normal development of the vertebrate brain, influencing diverse processes such as neuronal migration, myelin formation, axonal maturation, and dendritic outgrowth. We have identified basic transcription element-binding protein (BTEB), a small GC box-binding protein, as a T-3-regulated gene in developing rat brain. BTEB mRNA levels in cerebral cortex exhibit developmental regulation and thyroid hormone dependence. T-3 regulation of BTEB mRNA is neural cell specific, 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, suggesting that the regulation of this gene is specific to the TR beta 1 isoform, 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 suggesting 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 expression of acetylcholinesterase activity.