Journal Article

α and β Thyroid Hormone Receptor (TR) Gene Expression during Auditory Neurogenesis: Evidence for TR Isoform-Specific Transcriptional Regulation in vivo

Young, W. Scott, Bradley, David J., Towle, Howard C.

1994

Overview

Clinicians have long recognized that congenital deficiency of iodine (a component of thyroid hormone) somehow damages the human embryonic nervous system, causing sensori-neural deafness. Recently, a deletion encompassing most of the human β thyroid hormone receptor (TRβ) gene has been found in children who are neurologically normal except for one striking defect: profound sensori-neural deafness. We now show that the TRβ gene is prominently expressed very early in rat inner ear development. This expression is remarkable because both TRβ1 and TRβ2 mRNAs are restricted, as early as embryonic day 12.5, to that portion of the embryonic inner ear that gives rise to the cochlea, the structure responsible for converting sound into neural impulses. The timing of this expression, when correlated with human inner ear development, raises the possibility that TRs may act in human ontogenesis earlier than previously suspected. These results provide a rare correlation between a specific human neurologic deficit (deafness) and transcription factor expression in a highly discrete embryonic cell population (ventral otocyst). TRα gene expression is also prominent in the developing cochlea, but, in contrast to the restricted pattern of TRβ gene expression, TRα1 and TRα2 transcripts are also found in inner ear structures responsible for balance. Deafness in children homozygous for a large deletion in the TRβ gene suggests that cochlear α1 TRs cannot functionally compensate for the absence of TRβ1 and TRβ2. The developing inner ear may, therefore, represent an example of TR isoform-specific transcriptional regulation in vivo.

• Publisher: National Academy of Sciences of the United States of America,National Acad Sciences
• Subject: Animals / Cochlea / Cochlea - embryology / Cochlea - innervation / Cochlea - metabolism / Dams / Deafness / Deafness - genetics / Ear, Inner - embryology / Ear, Inner - innervation / Ear, Inner - metabolism / Female / Gene Expression Regulation / Genes / Humans / Inner ear / Messenger RNA / Polymerase chain reaction / Pregnancy / Rats / Rats, Sprague-Dawley / Receptors, Thyroid Hormone - genetics / RNA / RNA, Messenger - genetics / RNA, Messenger - metabolism / Thyroid hormones / Transcriptional Activation