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Gene Review

Foxn1  -  forkhead box N1

Mus musculus

Synonyms: D11Bhm185e, Fkh19, Forkhead box protein N1, HFH-11, HNF-3/forkhead homolog 11, ...
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Disease relevance of Foxn1


High impact information on Foxn1

  • However, subsequent differentiation of primitive precursor cells into subcapsular, cortical, and medullary epithelial cells of the postnatal thymus did depend on activity of the whn gene [2].
  • With the use of a targeted disruption of the whn gene, which recapitulates the phenotype of the athymic nude mouse, the WHN transcription factor was shown to be the product of the nude locus [2].
  • The pleiotropic nude phenotype which affects the hair, skin, and thymus suggests that whn plays a pivotal role in the development and/or maintenance of these organs [3].
  • These results establish whn as a key regulatory factor involved in maintaining the balance between keratinocyte growth and differentiation [3].
  • These experiments provide insights into Foxn1-dependent and Foxn1-independent stromal cell development and demonstrate the value of this chimeric approach to analyzing gene function in thymus epithelium [4].

Biological context of Foxn1

  • However, the endodermal cells of the thymus/parathyroid rudiments fail to maintain the expression of the parathyroid-specific gene Gcm2 and the thymus-specific gene Foxn1 and subsequently undergo abnormal apoptosis, leading to a complete disappearance of organ primordia by E12 [5].
  • Loss-of-function mutations in Whn (Hfh11, Foxn1), a winged-helix/forkhead transcription factor, cause the nude phenotype, which is characterized by the abnormal morphogenesis of the epidermis, hair follicles, and thymus [6].
  • Mutations in Foxn1 cause the nude phenotype [7].
  • In this paper we describe the production and analysis of mice carrying a 110-kb transgene that encompasses the wild-type Foxn1 genomic locus [7].
  • We show that in the hair follicles, transgenic mice with increased Foxn1 gene dosage exhibited increased Foxn1 expression that was restricted correctly to the nascent, post-mitotic cells of the differentiating hair cortex and hair cuticle lineages [7].

Anatomical context of Foxn1

  • Here, we provide an overview of what is known on the role of Foxn1 in mammalian skin biology, its expression patterns in the hair follicle, its influence on hair follicle function, and onychocyte differentiation [8].
  • To probe the function of postnatal progenitors, a conditional mutant allele of Foxn1 was reverted to wild-type function in single epithelial cells in vivo [9].
  • To delineate the biochemical pathway of Whn, we investigated its upstream regulation and downstream effects using primary keratinocytes from wild-type and transgenic mice [6].
  • Both Vegf-A alleles were deleted in TECs by a complementation strategy termed nude mouse [mutated in the transcription factor Foxn1 (forkhead box N1)] blastocyst complementation [4].
  • The nude mouse lacks functional T cells and other skin defects due to the absence of Foxn1 transcription factor [10].

Associations of Foxn1 with chemical compounds

  • IL-7 expression is initiated in the thymic fated domain of the early primordium by embryonic day 11.5 and is expressed in a Foxn1-independent pathway [11].
  • The transgenic animals express whn from the involucrin promoter, which is active in keratinocytes undergoing terminal differentiation [6].
  • We report here on the use of butylated hydroxytoluene (BHT)-mediated lung injury to demonstrate that HFH-11 protein and RNA levels were markedly increased throughout the period of lung repair [12].
  • In this method, one-cell embryos are arrested at metaphase by treatment with nocodazole, and whn exitting from the mitotic phase, two nuclei were formed in a single karyocyte following treatment with 6-dimethylaminopurine (6-DMAP) [13].

Regulatory relationships of Foxn1

  • BMP4 also acts directly on the thymic stroma to up-regulate the stroma-specific transcription factor Foxn1 and stroma-expressed chemokines [14].

Other interactions of Foxn1

  • The developing third pouch in Hoxa3(+/-)Pax1(-/-) compound mutants initiates normal expression of the parathyroid-specific Gcm2 and thymus-specific Foxn1 genes [15].
  • Before the start of differentiation, Whn levels were suppressed by the p42/p44 mitogen-activated protein kinase cascade, and this signaling pathway was rapidly inactivated as differentiation began [6].
  • Thus, as keratinocytes commit to terminal differentiation, mitogen-activated protein kinase signaling decreases, which permits the induction of Whn; Whn then activates early features of the differentiation program [6].
  • Our results reveal Foxn1 as an essential regulator of tissue assembly in the growing hair shaft and implicate Dsc2 as a downstream effector of this activity [16].
  • In an attempt to elucidate the role of the nude mutation on collagen production in skeletal muscles, we have measured collagen levels in several muscles of C57BL/10 nu/nu mice and compared them with mdx nu/nu and Foxn1+/+ control mice [10].

Analytical, diagnostic and therapeutic context of Foxn1


  1. Whn and mHa3 are components of the genetic hierarchy controlling hair follicle differentiation. Meier, N., Dear, T.N., Boehm, T. Mech. Dev. (1999) [Pubmed]
  2. Two genetically separable steps in the differentiation of thymic epithelium. Nehls, M., Kyewski, B., Messerle, M., Waldschütz, R., Schüddekopf, K., Smith, A.J., Boehm, T. Science (1996) [Pubmed]
  3. The product of the mouse nude locus, Whn, regulates the balance between epithelial cell growth and differentiation. Brissette, J.L., Li, J., Kamimura, J., Lee, D., Dotto, G.P. Genes Dev. (1996) [Pubmed]
  4. Gene targeting of VEGF-A in thymus epithelium disrupts thymus blood vessel architecture. Müller, S.M., Terszowski, G., Blum, C., Haller, C., Anquez, V., Kuschert, S., Carmeliet, P., Augustin, H.G., Rodewald, H.R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Patterning of the third pharyngeal pouch into thymus/parathyroid by Six and Eya1. Zou, D., Silvius, D., Davenport, J., Grifone, R., Maire, P., Xu, P.X. Dev. Biol. (2006) [Pubmed]
  6. Role of the nude gene in epithelial terminal differentiation. Baxter, R.M., Brissette, J.L. J. Invest. Dermatol. (2002) [Pubmed]
  7. Complete rescue of the nude mutant phenotype by a wild-type Foxn1 transgene. Cunliffe, V.T., Furley, A.J., Keenan, D. Mamm. Genome (2002) [Pubmed]
  8. Learning from nudity: lessons from the nude phenotype. Mecklenburg, L., Tychsen, B., Paus, R. Exp. Dermatol. (2005) [Pubmed]
  9. Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Bleul, C.C., Corbeaux, T., Reuter, A., Fisch, P., Mönting, J.S., Boehm, T. Nature (2006) [Pubmed]
  10. Nude mutation influences limb skeletal muscle development. Morrison, J., Partridge, T., Bou-Gharios, G. Matrix Biol. (2005) [Pubmed]
  11. Ontogeny and regulation of IL-7-expressing thymic epithelial cells. Zamisch, M., Moore-Scott, B., Su, D.M., Lucas, P.J., Manley, N., Richie, E.R. J. Immunol. (2005) [Pubmed]
  12. Differential expression of forkhead box transcription factors following butylated hydroxytoluene lung injury. Kalinichenko, V.V., Lim, L., Shin, B., Costa, R.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  13. Role of the first mitosis in the remodeling of the parental genomes in mouse embryos. Liu, H.L., Hara, K.T., Aoki, F. Cell Res. (2005) [Pubmed]
  14. BMP4 acts upstream of FGF in modulating thymic stroma and regulating thymopoiesis. Tsai, P.T., Lee, R.A., Wu, H. Blood (2003) [Pubmed]
  15. Hoxa3 and pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis. Su, D., Ellis, S., Napier, A., Lee, K., Manley, N.R. Dev. Biol. (2001) [Pubmed]
  16. Foxn1 is required for tissue assembly and desmosomal cadherin expression in the hair shaft. Johns, S.A., Soullier, S., Rashbass, P., Cunliffe, V.T. Dev. Dyn. (2005) [Pubmed]
  17. Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues. Ye, H., Kelly, T.F., Samadani, U., Lim, L., Rubio, S., Overdier, D.G., Roebuck, K.A., Costa, R.H. Mol. Cell. Biol. (1997) [Pubmed]
  18. Laser capture microdissection-based expression profiling identifies PD1-ligand as a target of the nude locus gene product. Bleul, C.C., Boehm, T. Eur. J. Immunol. (2001) [Pubmed]
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