PAX8, TITF1, and FOXE1 gene expression patterns during human development: new insights into human thyroid development and thyroid dysgenesis-associated malformations

J Clin Endocrinol Metab. 2005 Jan;90(1):455-62. doi: 10.1210/jc.2004-1358. Epub 2004 Oct 19.

Abstract

Thyroid dysgenesis (TD) is responsible for most cases of congenital hypothyroidism, a condition that affects about one in 4000 newborns. Mutations in PAX8, TITF1, or FOXE1 may account for congenital hypothyroidism in patients with either isolated TD or TD with associated malformations involving kidney, lung, forebrain, and palate. Pax8, titf1, and foxe1 are expressed in the mouse thyroid bud as soon as it differentiates on the pharyngeal floor. Because the spatio-temporal expression of these genes is unknown in humans, we decided to study them at different stages of human embryonic and fetal development. PAX8 and TITF1 were first expressed in the median thyroid primordium. Interestingly, PAX8 was also expressed in the thyroglossal duct and the ultimobranchial bodies. Human FOXE1 expression was detected later than in the mouse. PAX8 was also expressed in the developing central nervous system and kidney, including the ureteric bud and the main collecting ducts. TITF1 was expressed in the ventral forebrain and lung. FOXE1 expression was detected in the oropharyngeal epithelium and thymus. In conclusion, the expression patterns described here show some differences from those reported in the mouse. They explain the malformations associated with TD in patients carrying PAX8, TITF1, and FOXE1 gene mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics*
  • Embryonic Development
  • Fetal Development
  • Forkhead Transcription Factors
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Mice
  • Nuclear Proteins / genetics*
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors
  • Repressor Proteins / genetics*
  • Thyroglobulin / analysis
  • Thyroid Gland / abnormalities*
  • Thyroid Gland / embryology*
  • Thyroid Nuclear Factor 1
  • Trans-Activators / genetics*
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • FOXE1 protein, human
  • Forkhead Transcription Factors
  • Nkx2-1 protein, mouse
  • Nuclear Proteins
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Paired Box Transcription Factors
  • Pax8 protein, mouse
  • Repressor Proteins
  • Thyroid Nuclear Factor 1
  • Trans-Activators
  • Transcription Factors
  • Thyroglobulin