title: Thyroid transcription factors in development, differentiation and disease.
abstract: Identification of the thyroid transcription factors (TTFs), NKX2-1, FOXE1, PAX8 and HHEX, has considerably advanced our understanding of thyroid development, congenital thyroid disorders and thyroid cancer. The TTFs are fundamental to proper formation of the thyroid gland and for maintaining the functional differentiated state of the adult thyroid; however, they are not individually required for precursor cell commitment to a thyroid fate. Although knowledge of the mechanisms involved in thyroid development has increased, the full complement of genes involved in thyroid gland specification and the signals that trigger expression of the genes that encode the TTFs remain unknown. The mechanisms involved in thyroid organogenesis and differentiation have provided clues to identifying the genes that are involved in human congenital thyroid disorders and thyroid cancer. Mutations in the genes that encode the TTFs, as well as polymorphisms and epigenetic modifications, have been associated with thyroid pathologies. Here, we summarize the roles of the TTFs in thyroid development and the mechanisms by which they regulate expression of the genes involved in thyroid differentiation. We also address the implications of mutations in TTFs in thyroid diseases and in diseases not related to the thyroid gland.
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas, and Universidad Autónoma de Madrid, Arturo Duperier 4, Madrid 28029, Spain.
authors.forename: Lara P
authors.initials: LP
authors.lastname: Fernández
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas, and Universidad Autónoma de Madrid, Arturo Duperier 4, Madrid 28029, Spain.
authors.forename: Arístides
authors.initials: A
authors.lastname: López-Márquez
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas, and Universidad Autónoma de Madrid, Arturo Duperier 4, Madrid 28029, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Santisteban
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000254:growth & development* / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; C078492:HHEX protein, human; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors