A unique combination of transcription factors controls differentiation of thyroid cells.
The thyroid follicular cell type is devoted to the synthesis of thyroid hormones. Several genes, whose protein products are essential for efficient hormone biosynthesis, are uniquely expressed in this cell type. A set of transcriptional regulators, unique to the thyroid follicular cell type, has been identified as responsible for thyroid specific gene expression; it comprises three transcription factors, named TTF-1, TTF-2, and Pax8, each of which is expressed also in cell types different from the thyroid follicular cells. However, the combination of these factors is unique to the thyroid hormone producing cells, strongly suggesting that they play an important role in differentiation of these cells. An overview of the molecular and biological features of these transcription factors is presented here. Data demonstrating that all three play also an important role in early thyroid development, at stages preceding expression of the differentiated phenotype, are also reviewed. The wide temporal expression, from the beginning of thyroid organogenesis to the adult state, is suggestive of a recycling of the thyroid-specific transcription factors, that is, the control of different sets of target genes at diverse developmental stages. The identification of molecular mechanisms leading to specific gene expression in thyroid cells renders this cell type an interesting model in which to address several aspects of cell differentiation and organogenesis.
Damante
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Dipartimento di Scienze e Tecnologie Biomediche Università di Udine.
Tell
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Di Lauro
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D000818:Animals; D002454:Cell Differentiation; D003001:Cloning, Molecular; D003409:Congenital Hypothyroidism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D051858:Forkhead Transcription Factors; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000502:physiology; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology
D004268:DNA-Binding Proteins; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors