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

Robert J Denver,Lydia Ouellet,Denis Furling,Akira Kobayashi,Yoshiaki Fujii-Kuriyama,Jack Puymirat

doi:10.1074/jbc.274.33.23128

Abstract

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) beta1 but not in cells expressing TRalpha1, suggesting that the regulation of this gene is specific to the TRbeta1 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.

Highlights

Thyroid hormone (3,5,3؅-triiodothyronine; T3) is essential for normal development of the vertebrate brain, influencing diverse processes such as neuronal migration, myelin formation, axonal maturation, and dendritic outgrowth
Thyroid Hormone Dependence of basic transcription element-binding protein (BTEB) mRNA Expression in Developing Rat Cerebral Hemisphere—Hypothyroidism induced by treatment with the goitrogen PTU and the restoration of euthyroidism in rats treated with PTU ϩ T3 was confirmed by radioimmunoassay
The expression of BTEB mRNA in the developing rat brain depends on thyroid status; the induction of hypothyroidism in neonatal pups resulted in reduced expression that was restored by T3 replacement therapy

Summary

Introduction

Thyroid hormone (3,5,3؅-triiodothyronine; T3) 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 T3-regulated gene in developing rat brain. T3 rapidly up-regulated BTEB mRNA in neuro-2a cells engineered to express thyroid hormone receptor (TR) ␤1 but not in cells expressing TR␣1, suggesting that the regulation of this gene is specific to the TR␤1 isoform. 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. Differential screening experiments have identified several T3-regulated genes in the rodent CNS (10 –14); but, roles for the protein products of these genes in T3 action on the brain have not been established. While BTEB mRNA is ubiquitously expressed in the rat, the mRNA appears to be translated only in the brain [19]

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