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Gene Review

Foxe3  -  forkhead box E3

Mus musculus

Synonyms: FREAC8, Forkhead box protein E3, dyl, rct
 
 
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Disease relevance of Foxe3

  • Mutations in the Foxe3 gene are the cause of the mouse mutation dysgenetic lens (dyl) and in humans, mutation in FOXE3 leads to anterior segment dysgenesis and cataracts [1].
 

High impact information on Foxe3

  • Foxe3 encodes a winged helix-forkhead transcription factor that is initially expressed in the developing brain and in the lens placode and later restricted exclusively to the anterior lens epithelium [2].
  • Regulation of ocular lens development by Smad-interacting protein 1 involving Foxe3 activation [3].
  • A 6.2 kb Foxe3 promoter region controlled lacZ transgene expression in the developing lens, where major and minor lens elements were identified upstream of -1.26 kb [3].
  • We conclude that Mab21l1 expression dependent on PAX6 is essential for lens placode growth and for formation of the lens vesicle; lack of Mab21l1 expression causes reduced expression of Foxe3 in a cell-autonomous manner [4].
  • This manifested as exacerbated lens development defects and lower levels of Pax6 and Foxe3 expression in Tfr7/Tfr7, Bmp7(+/-) mice when compared with Tfr7/Tfr7 mice alone [5].
 

Biological context of Foxe3

  • Interestingly, deletion of the ectoderm enhancer causes loss of expression of Foxe3, a transcription factor gene mutated in the dysgenetic lens mouse [6].
  • We have identified mutations in Foxe3 that cosegregate with the dyl phenotype and are a likely cause of the mutant phenotype [7].
  • During development Foxe3 is expressed in all undifferentiated lens tissues, and is turned off upon fiber cell differentiation [7].
  • Foxe3 is required for morphogenesis and differentiation of the anterior segment of the eye and is sensitive to Pax6 gene dosage [8].
  • PURPOSE: To evaluate the importance in anterior segment dysgenesis of genetic variation in Foxe3, a gene encoding a forkhead transcription factor specifically expressed in the lens [9].
 

Associations of Foxe3 with chemical compounds

 

Other interactions of Foxe3

  • Head ectoderm expression of Foxe3 is absent in Rx-/- and Small eye embryos indicating that Rx and Pax6 activity are necessary for Foxe3 expression [7].

References

  1. Expression of FoxE4 and Rx visualizes the timing and dynamics of critical processes taking place during initial stages of vertebrate eye development. Zilinski, C., Brownell, I., Hashimoto, R., Medina-Martinez, O., Swindell, E.C., Jamrich, M. Dev. Neurosci. (2004) [Pubmed]
  2. Severe defects in proliferation and differentiation of lens cells in Foxe3 null mice. Medina-Martinez, O., Brownell, I., Amaya-Manzanares, F., Hu, Q., Behringer, R.R., Jamrich, M. Mol. Cell. Biol. (2005) [Pubmed]
  3. Regulation of ocular lens development by Smad-interacting protein 1 involving Foxe3 activation. Yoshimoto, A., Saigou, Y., Higashi, Y., Kondoh, H. Development (2005) [Pubmed]
  4. Cell-autonomous involvement of Mab21l1 is essential for lens placode development. Yamada, R., Mizutani-Koseki, Y., Hasegawa, T., Osumi, N., Koseki, H., Takahashi, N. Development (2003) [Pubmed]
  5. Fgf receptor signaling plays a role in lens induction. Faber, S.C., Dimanlig, P., Makarenkova, H.P., Shirke, S., Ko, K., Lang, R.A. Development (2001) [Pubmed]
  6. The upstream ectoderm enhancer in Pax6 has an important role in lens induction. Dimanlig, P.V., Faber, S.C., Auerbach, W., Makarenkova, H.P., Lang, R.A. Development (2001) [Pubmed]
  7. Forkhead Foxe3 maps to the dysgenetic lens locus and is critical in lens development and differentiation. Brownell, I., Dirksen, M., Jamrich, M. Genesis (2000) [Pubmed]
  8. Foxe3 is required for morphogenesis and differentiation of the anterior segment of the eye and is sensitive to Pax6 gene dosage. Blixt, A., Landgren, H., Johansson, B.R., Carlsson, P. Dev. Biol. (2007) [Pubmed]
  9. Foxe3 haploinsufficiency in mice: a model for Peters' anomaly. Ormestad, M., Blixt, A., Churchill, A., Martinsson, T., Enerbäck, S., Carlsson, P. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  10. Ontogeny of alpha-crystallin polypeptides during the lens development of a mutant mouse. Brahma, S.K., Sanyal, S. Curr. Eye Res. (1987) [Pubmed]
 
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