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Gene Review

Tfap2a  -  transcription factor AP-2, alpha

Mus musculus

Synonyms: AP-2, AP-2 alpha, AP-2 transcription factor, AP2-alpha, AP2alpha, ...
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Disease relevance of Tcfap2a


Psychiatry related information on Tcfap2a

  • Together, the adult brain regions with AP-2 expressing neurons are notable for their importance in pathways that integrate sensory and neuroendocrine information for regulation of reproductive, social, and feeding behaviors [4].
  • Sexually dimorphic expression of AP-2 was seen in the bed nucleus of the stria terminalis, a forebrain region required for regulation of gender-specific reproductive and social behaviors [4].

High impact information on Tcfap2a


Chemical compound and disease context of Tcfap2a

  • During retinoic acid (RA)-mediated differentiation of P19 embryonal carcinoma cells into neuroectodermal cell types that include immunohistochemically defined neurons and astrocytes, we observed a strong induction of AP-2 transcripts and protein [8].

Biological context of Tcfap2a

  • Furthermore, with the exception of Tcfap2a, these genes are also expressed in unfertilized oocytes, indicating that they may be important for oogenesis, maternal-effect functions, or both [9].
  • Using ENU-induced mutagenesis, we discovered a new dominant Tcfap2a mutant named Doarad ( Dor) that has a missense mutation in the PY motif of its transactivation domain, leading to a misshapen malleus, incus, and stapes without any other observable phenotype [1].
  • For example, transcription factor AP-2alpha ( Tcfap2a) null homozygote mice show a large spectrum of developmental defects, among them missing middle ear bones and tympanic ring [1].
  • To assess the contribution of individual endocytic proteins to the assembly of clathrin coated pits, we depleted the clathrin heavy chain and the alpha-adaptin subunit of AP-2 in HeLa-cells using RNA interference [10].
  • RESULTS: Expression of the NCC marker AP-2 revealed an extensive reduction in migratory NCC, however the rates of cell proliferation and apoptosis were unaffected, and do not account for the Sp(2H) NCC-associated heart defects [11].

Anatomical context of Tcfap2a

  • Moreover, neural crest induction occurs normally in zebrafish tfap2a and mouse Tcfap2a mutant embryos, so it was unclear if a requirement for Tfap2a in this process has been evolutionarily conserved [12].
  • Indeed, the size of branchial arches and the frontonasal mass of mutant embryos was comparable to that of WT embryos, and the pattern of expression of Ap2, a marker of migrating CNC cells, was normal [13].
  • Redundant activities of Tfap2a and Tfap2c are required for neural crest induction and development of other non-neural ectoderm derivatives in zebrafish embryos [12].
  • Analysis of animals lacking AP-2alpha revealed a dramatic decrease in forebrain LHRH neurons between E13.5 and E14.5, correlating with normal onset of AP-2 expression in LHRH neurons as they entered the central nervous system [14].
  • AP-2 has been characterized previously as a unique 52 x 10(3) M(r) transcription activator encoded by a single gene that is expressed in a restricted pattern during embryonic morphogenesis of the peripheral nervous system, face, skin and nephric tissues [15].

Associations of Tcfap2a with chemical compounds


Regulatory relationships of Tcfap2a


Other interactions of Tcfap2a


Analytical, diagnostic and therapeutic context of Tcfap2a


  1. An ENU-induced mutation in AP-2alpha leads to middle ear and ocular defects in Doarad mice. Ahituv, N., Erven, A., Fuchs, H., Guy, K., Ashery-Padan, R., Williams, T., de Angelis, M.H., Avraham, K.B., Steel, K.P. Mamm. Genome (2004) [Pubmed]
  2. Neural tube, skeletal and body wall defects in mice lacking transcription factor AP-2. Zhang, J., Hagopian-Donaldson, S., Serbedzija, G., Elsemore, J., Plehn-Dujowich, D., McMahon, A.P., Flavell, R.A., Williams, T. Nature (1996) [Pubmed]
  3. In vivo interferon regulatory factor 3 tumor suppressor activity in B16 melanoma tumors. Duguay, D., Mercier, F., Stagg, J., Martineau, D., Bramson, J., Servant, M., Lin, R., Galipeau, J., Hiscott, J. Cancer Res. (2002) [Pubmed]
  4. Cell type-specific and sexually dimorphic expression of transcription factor AP-2 in the adult mouse brain. Coelho, D.J., Sims, D.J., Ruegg, P.J., Minn, I., Muench, A.R., Mitchell, P.J. Neuroscience (2005) [Pubmed]
  5. Transcription factor AP-2 essential for cranial closure and craniofacial development. Schorle, H., Meier, P., Buchert, M., Jaenisch, R., Mitchell, P.J. Nature (1996) [Pubmed]
  6. Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta. Moser, M., Pscherer, A., Roth, C., Becker, J., Mücher, G., Zerres, K., Dixkens, C., Weis, J., Guay-Woodford, L., Buettner, R., Fässler, R. Genes Dev. (1997) [Pubmed]
  7. Transcription factor AP-2 is expressed in neural crest cell lineages during mouse embryogenesis. Mitchell, P.J., Timmons, P.M., Hébert, J.M., Rigby, P.W., Tjian, R. Genes Dev. (1991) [Pubmed]
  8. Cell type-specific regulation of expression of transcription factor AP-2 in neuroectodermal cells. Philipp, J., Mitchell, P.J., Malipiero, U., Fontana, A. Dev. Biol. (1994) [Pubmed]
  9. Analysis of transcription factor AP-2 expression and function during mouse preimplantation development. Winger, Q., Huang, J., Auman, H.J., Lewandoski, M., Williams, T. Biol. Reprod. (2006) [Pubmed]
  10. Effect of clathrin heavy chain- and alpha-adaptin-specific small inhibitory RNAs on endocytic accessory proteins and receptor trafficking in HeLa cells. Hinrichsen, L., Harborth, J., Andrees, L., Weber, K., Ungewickell, E.J. J. Biol. Chem. (2003) [Pubmed]
  11. Decreased neural crest stem cell expansion is responsible for the conotruncal heart defects within the splotch (Sp(2H))/Pax3 mouse mutant. Conway, S.J., Bundy, J., Chen, J., Dickman, E., Rogers, R., Will, B.M. Cardiovasc. Res. (2000) [Pubmed]
  12. Redundant activities of Tfap2a and Tfap2c are required for neural crest induction and development of other non-neural ectoderm derivatives in zebrafish embryos. Li, W., Cornell, R.A. Dev. Biol. (2007) [Pubmed]
  13. Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest. Mori-Akiyama, Y., Akiyama, H., Rowitch, D.H., de Crombrugghe, B. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  14. Transcription factor activator protein-2 is required for continued luteinizing hormone-releasing hormone expression in the forebrain of developing mice. Kramer, P.R., Krishnamurthy, R., Mitchell, P.J., Wray, S. Endocrinology (2000) [Pubmed]
  15. Cloning and characterization of a second AP-2 transcription factor: AP-2 beta. Moser, M., Imhof, A., Pscherer, A., Bauer, R., Amselgruber, W., Sinowatz, F., Hofstädter, F., Schüle, R., Buettner, R. Development (1995) [Pubmed]
  16. AP-2alpha transcription factor is required for early morphogenesis of the lens vesicle. West-Mays, J.A., Zhang, J., Nottoli, T., Hagopian-Donaldson, S., Libby, D., Strissel, K.J., Williams, T. Dev. Biol. (1999) [Pubmed]
  17. Association of epidermal growth factor receptors with coated pit adaptins via a tyrosine phosphorylation-regulated mechanism. Nesterov, A., Kurten, R.C., Gill, G.N. J. Biol. Chem. (1995) [Pubmed]
  18. Reduction of adrenal and kidney epinephrine and phenylethanolamine N-methyltransferase in AP-2 knockout mouse fetuses. Kennedy, B., Enns, R., Nelson, D., Williams, T., Bao, X., Ziegler, M.G. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
  19. Regulation of AP-2 and apoptosis in developing eye in a vitamin A-deficiency model. Zhou, J., Kochhar, D.M. Birth defects research. Part A, Clinical and molecular teratology. (2003) [Pubmed]
  20. A proline-rich transcriptional activation domain in murine HOXD-4 (HOX-4.2). Rambaldi, I., Kovàcs, E.N., Featherstone, M.S. Nucleic Acids Res. (1994) [Pubmed]
  21. AP2-dependent signals from the ectoderm regulate craniofacial development in the zebrafish embryo. Knight, R.D., Javidan, Y., Zhang, T., Nelson, S., Schilling, T.F. Development (2005) [Pubmed]
  22. Transcription factor AP-2gamma regulates murine adenosine deaminase gene expression during placental development. Shi, D., Kellems, R.E. J. Biol. Chem. (1998) [Pubmed]
  23. Comparative analysis of AP-2 alpha and AP-2 beta gene expression during murine embryogenesis. Moser, M., Rüschoff, J., Buettner, R. Dev. Dyn. (1997) [Pubmed]
  24. Characterisation of the Mouse Vasoactive Intestinal Peptide Receptor Type 2 Gene, Vipr2, and Identification of a Polymorphic LINE-1-like Sequence That Confers Altered Promoter Activity. Steel, G., Lutz, E.M. J. Neuroendocrinol. (2007) [Pubmed]
  25. Regulation of Hoxa2 in cranial neural crest cells involves members of the AP-2 family. Maconochie, M., Krishnamurthy, R., Nonchev, S., Meier, P., Manzanares, M., Mitchell, P.J., Krumlauf, R. Development (1999) [Pubmed]
  26. Molecular cloning and characterization of AP-2 epsilon, a fifth member of the AP-2 family. Tummala, R., Romano, R.A., Fuchs, E., Sinha, S. Gene (2003) [Pubmed]
  27. Association and colocalization of Eps15 with adaptor protein-2 and clathrin. van Delft, S., Schumacher, C., Hage, W., Verkleij, A.J., van Bergen en Henegouwen, P.M. J. Cell Biol. (1997) [Pubmed]
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