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Gene Review

Foxd3  -  forkhead box D3

Mus musculus

Synonyms: CWH3, Forkhead box protein D3, Genesis, HFH-2, HNF3/FH transcription factor genesis, ...
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Disease relevance of Foxd3

  • Extensive Northern analysis of Genesis found that the message was exclusively expressed in embryonic stem cells or their malignant equivalent, embryonal carcinoma cells [1].
  • Based on that finding, Genesis was retrovirally transduced into pluripotent N-Tera-2 clone D1 (NT2/D1) teratocarcinoma cells, which are a well-described in vitro model of neural development [2].

High impact information on Foxd3

  • These results establish Foxd3 as a factor required for the maintenance of progenitor cells in the mammalian embryo [3].
  • Together these results suggest Foxd3 can function independently of Slug and RhoB to promote the development of neural crest cells from neural tube progenitors [4].
  • We show that misexpression of Foxd3 in the chick neural tube promotes a neural crest-like phenotype and suppresses interneuron differentiation [4].
  • We previously showed, using differential expression screening and in situ hybridization that Vanin-1, which encodes a glycosylphosphatidylinositol-linked membrane-associated pantetheinase, is expressed in a sex-specific manner during fetal gonad development in mice (Bowles, J., Bullejos, M., and Koopman, P. (2000) Genesis 27, 124-135) [5].
  • DNA sequences that Genesis protein would interact with were characterized and were found to contain a consensus similar to that found in an embryonic stem cell enhancer sequence [1].

Biological context of Foxd3

  • Re-expression of the ES-specific gene Foxd3 from somatic-derived chromosomes suggested that the somatic nucleus had been reprogrammed [6].
  • In this study in situ cRNA hybridization experiments revealed that Genesis was expressed during embryogenesis only in developing neural crest cells [2].

Anatomical context of Foxd3


Associations of Foxd3 with chemical compounds

  • Although RA-induced expression of neuronal differentiation markers was not influenced by forced overexpression of Genesis in NT2-D1 cells, proliferation of Genesis-transduced cells continued following RA treatment [2].
  • A novel repressor of the Winged Helix (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis (also called HFH2), was previously found to be exclusively expressed in primitive embryonic cell lines [2].

Other interactions of Foxd3


Analytical, diagnostic and therapeutic context of Foxd3

  • The subcellular localization of Foxd3 varies with fat content in the diet; with a high fat diet the protein is found primarily in the cytoplasm while a low fat diet results in nuclear localization [8].


  1. Genesis, a winged helix transcriptional repressor with expression restricted to embryonic stem cells. Sutton, J., Costa, R., Klug, M., Field, L., Xu, D., Largaespada, D.A., Fletcher, C.F., Jenkins, N.A., Copeland, N.G., Klemsz, M., Hromas, R. J. Biol. Chem. (1996) [Pubmed]
  2. Genesis, a Winged Helix transcriptional repressor, has embryonic expression limited to the neural crest, and stimulates proliferation in vitro in a neural development model. Hromas, R., Ye, H., Spinella, M., Dmitrovsky, E., Xu, D., Costa, R.H. Cell Tissue Res. (1999) [Pubmed]
  3. Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo. Hanna, L.A., Foreman, R.K., Tarasenko, I.A., Kessler, D.S., Labosky, P.A. Genes Dev. (2002) [Pubmed]
  4. The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate. Dottori, M., Gross, M.K., Labosky, P., Goulding, M. Development (2001) [Pubmed]
  5. The transcription factors steroidogenic factor-1 and SOX9 regulate expression of Vanin-1 during mouse testis development. Wilson, M.J., Jeyasuria, P., Parker, K.L., Koopman, P. J. Biol. Chem. (2005) [Pubmed]
  6. Multipotentiality of neuronal cells after spontaneous fusion with embryonic stem cells and nuclear reprogramming in vitro. Pells, S., Di Domenico, A.I., Gallagher, E.J., McWhir, J. Cloning Stem Cells (2002) [Pubmed]
  7. Foxd3 is required in the trophoblast progenitor cell lineage of the mouse embryo. Tompers, D.M., Foreman, R.K., Wang, Q., Kumanova, M., Labosky, P.A. Dev. Biol. (2005) [Pubmed]
  8. Expression and shifting subcellular localization of the transcription factor, Foxd3, in embryonic and adult pancreas. Perera, H.K., Caldwell, M.E., Hayes-Patterson, D., Teng, L., Peshavaria, M., Jetton, T.L., Labosky, P.A. Gene Expr. Patterns (2006) [Pubmed]
  9. Forced expression of Genesis, a winged helix transcriptional repressor isolated from embryonic stem cells, blocks granulocytic differentiation of 32D myeloid cells. Xu, D., Yoder, M., Sutton, J., Hromas, R. Leukemia (1998) [Pubmed]
  10. The winged helix transcription factor Hfh2 is expressed in neural crest and spinal cord during mouse development. Labosky, P.A., Kaestner, K.H. Mech. Dev. (1998) [Pubmed]
  11. Maturation of bone marrow lymphocytes. III. Genesis of Fc receptor-bearing "null" cells and B lymphocytes subtypes defined by concomitant expression of surface IgM, Fc, and complement receptors. Chan, F.P., Osmond, D.G. Cell. Immunol. (1979) [Pubmed]
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