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Gene Review

Foxe1  -  forkhead box E1

Mus musculus

Synonyms: Forkhead box protein E1, TTF-2, Thyroid transcription factor 2, Titf2, thyroid transcription factor 2
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Disease relevance of Foxe1


High impact information on Foxe1

  • TTF-2 is a member of the forkhead/winged-helix domain transcription factor family, many of which are key regulators of embryogenesis [5].
  • We have recently cloned cDNA encoding a forkhead domain-containing transcription factor, TTF-2, and have located the position of the gene, designated Titf2, to mouse chromosome 4 (ref. 3). Titf2 is expressed in the developing thyroid, in most of the foregut endoderm and in craniopharyngeal ectoderm, including Rathke's pouch [2].
  • TTF-2 is a new forkhead domain-containing protein whose expression is restricted to the endodermal lining of the foregut and to the ectoderm that will give rise to the anterior pituitary [6].
  • In the thyroid, TTF-2 expression is down-regulated just before the onset of Tg and TPO gene expression, suggesting that this transcription factor plays the role in development of a negative controller of thyroid-specific gene expression [6].
  • The forkhead transcription factor FOXE1 is mutated in patients with Bamforth-Lazarus syndrome that exhibit hair follicle defects, suggesting a possible role for Foxe1 in hair follicle morphogenesis [1].

Biological context of Foxe1


Anatomical context of Foxe1

  • Moreover, by the generation of mouse mutants expressing Foxe1 exclusively in the thyroid primordium, we provide a better understanding of the role of Foxe1 in these cells in order to acquire the competence to migrate into the underlying mesenchyme [7].
  • Three genes, TTF1, TTF2, and PAX8, involved in thyroid gland development and migration have been identified [8].
  • Strikingly, TTF-1- and TTF-2-positive cells aberrantly develop in the presumptive trachea of Shh-/- embryos [9].
  • According to this expression, at E13.5, TTF-2 is present in endoderm derivatives, such as tongue, palate, epiglottis, pharynx, and oesophagus [3].
  • At embryonic day (E) 10.5, TTF-2 is expressed in Rathke's pouch, in thyroid, and in the epithelium of the pharyngeal wall and arches, whereas it is absent in the epithelium of the pharyngeal pouches [3].

Associations of Foxe1 with chemical compounds

  • Direct sequencing of the TTF-2 gene revealed polymorphisms in the length of the polyalanine tract [4].

Other interactions of Foxe1


  1. Requirement of the forkhead gene Foxe1, a target of sonic hedgehog signaling, in hair follicle morphogenesis. Brancaccio, A., Minichiello, A., Grachtchouk, M., Antonini, D., Sheng, H., Parlato, R., Dathan, N., Dlugosz, A.A., Missero, C. Hum. Mol. Genet. (2004) [Pubmed]
  2. A mouse model for hereditary thyroid dysgenesis and cleft palate. De Felice, M., Ovitt, C., Biffali, E., Rodriguez-Mallon, A., Arra, C., Anastassiadis, K., Macchia, P.E., Mattei, M.G., Mariano, A., Schöler, H., Macchia, V., Di Lauro, R. Nat. Genet. (1998) [Pubmed]
  3. Distribution of the titf2/foxe1 gene product is consistent with an important role in the development of foregut endoderm, palate, and hair. Dathan, N., Parlato, R., Rosica, A., De Felice, M., Di Lauro, R. Dev. Dyn. (2002) [Pubmed]
  4. Genetic analysis of TTF-2 gene in children with congenital hypothyroidism and cleft palate, congenital hypothyroidism, or isolated cleft palate. Tonacchera, M., Banco, M., Lapi, P., Di Cosmo, C., Perri, A., Montanelli, L., Moschini, L., Gatti, G., Gandini, D., Massei, A., Agretti, P., De Marco, G., Vitti, P., Chiovato, L., Pinchera, A. Thyroid (2004) [Pubmed]
  5. Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia. Clifton-Bligh, R.J., Wentworth, J.M., Heinz, P., Crisp, M.S., John, R., Lazarus, J.H., Ludgate, M., Chatterjee, V.K. Nat. Genet. (1998) [Pubmed]
  6. TTF-2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role in controlling the onset of differentiation. Zannini, M., Avantaggiato, V., Biffali, E., Arnone, M.I., Sato, K., Pischetola, M., Taylor, B.A., Phillips, S.J., Simeone, A., Di Lauro, R. EMBO J. (1997) [Pubmed]
  7. An integrated regulatory network controlling survival and migration in thyroid organogenesis. Parlato, R., Rosica, A., Rodriguez-Mallon, A., Affuso, A., Postiglione, M.P., Arra, C., Mansouri, A., Kimura, S., Di Lauro, R., De Felice, M. Dev. Biol. (2004) [Pubmed]
  8. Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice. Pohlenz, J., Dumitrescu, A., Zundel, D., Martiné, U., Schönberger, W., Koo, E., Weiss, R.E., Cohen, R.N., Kimura, S., Refetoff, S. J. Clin. Invest. (2002) [Pubmed]
  9. Genetic deletion of sonic hedgehog causes hemiagenesis and ectopic development of the thyroid in mouse. Fagman, H., Grände, M., Gritli-Linde, A., Nilsson, M. Am. J. Pathol. (2004) [Pubmed]
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