Distribution of the titf2/foxe1 gene product is consistent with an important role in the development of foregut endoderm, palate, and hair

Abstract

Titf2/foxe1 is a forkhead domain-containing gene expressed in the foregut, in the thyroid, and in the cranial ectoderm of the developing mouse. Titf2 null mice exhibit cleft palate and either a sublingual or completely absent thyroid gland. In humans, mutations of the gene encoding for thyroid transcription factor-2 (TTF-2) result in the Bamforth syndrome, characterized by thyroid agenesis, cleft palate, spiky hair, and choanal atresia. Here, we report a detailed expression pattern of TTF-2 protein during mouse embryogenesis and show its presence in structures where it has not been described yet. 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. According to this expression, at E13.5, TTF-2 is present in endoderm derivatives, such as tongue, palate, epiglottis, pharynx, and oesophagus. Later in embryogenesis, we detect TTF-2 in the choanae and whiskers. This pattern of expression helps to define the complex phenotype displayed by human patients. Finally, we show that TTF-2 is a phosphorylated protein. These results help to characterize the domains of TTF-2 expression, from early embryogenesis throughout organogenesis, providing more detail on the potential role of TTF-2 in the development of endoderm and ectoderm derived structures.

Expression and clinical significance of FOXE1 in papillary thyroid carcinoma

“…Numerous members of the forkhead family are potent transcriptional activators in the adult thyroid and are important in cell growth and differentiation (3,4), including FOXE1 which is important in the development and differentiation of thyroid follicular cells (5,6). In addition, a growing body of data have indicated that FOXE1 is important in the initiation of specific tumors, including pancreatic cancer, cutaneous squamous cell carcinoma and thyroid neoplasms (7)(8)(9).…”

A NovelFOXE1Mutation (R73S) in Bamforth–Lazarus Syndrome Causing Increased Thyroidal Gene Expression

“…FOXE1 was initially characterized as a thyroid-specific transcription factor that binds to both the thyroglobulin (TG) and thyroid peroxidase (TPO) gene promoters, two thyroid differentiation markers (2,3). During development, FOXE1 is expressed in the thyroid and oropharyngeal epithelium of humans and mice, and in the thymus of humans only (4,5). FOXE1 is also expressed in the adult human thyroid, as well as in the hair follicles and prepubertal testis (6).…”

Xenopus laevis FoxE1 is primarily expressed in the developing pituitary and thyroid

“…Many of these gene products are involved in regulation of gene transcription during development and several developmental disorders in humans are caused by mutations in Fox genes (Carlsson and Mahlapuu, 2002, Hromas and Costa, 1995, Kaufmann and Knochel, 1996. Members of the FoxE subfamily of Fox genes are expressed in the developing anterior ectoderm and endoderm (Blixt et al, 2000, Brownell et al, 2000, Dathan et al, 2002, Kenyon et al, 1999, Yu et al, 2002, Zannini et al, 1997. This subfamily includes mammalian Foxe1 (thyroid transcription factor 2 or TTF-2), Foxe3 and Xenopus FoxE4 (Xlens1 ).…”

“…This subfamily includes mammalian Foxe1 (thyroid transcription factor 2 or TTF-2), Foxe3 and Xenopus FoxE4 (Xlens1 ). Foxe1 is expressed in several developing ectodermal and endodermal derivatives of the head including the thyroid, Rathke's pouch, tongue, esophagus, epiglottis, pharynx, whiskers and nasal choanae (Dathan et al, 2002, Zannini et al, 1997. Foxe3 is primarily expressed in the developing lens ectoderm (Blixt et al, 2000, Brownell et al, 2000.…”