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Gene Review

Pitx3  -  paired-like homeodomain transcription...

Mus musculus

Synonyms: Homeobox protein PITX3, Paired-like homeodomain transcription factor 3, Pituitary homeobox 3, Ptx3, ak
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Disease relevance of Pitx3


Psychiatry related information on Pitx3

  • Thus, Pitx3 defines a pathway for survival of neurons that are implicated in PD and that are required for spontaneous locomotor activity [4].

High impact information on Pitx3


Chemical compound and disease context of Pitx3


Biological context of Pitx3


Anatomical context of Pitx3


Regulatory relationships of Pitx3


Other interactions of Pitx3

  • Cig30 and Pitx3 genes are arranged in a partially overlapping tail-to-tail array resulting in complementary transcripts [17].
  • A recent report described a deletion in the intergenic region between Gbf1 and Pitx3 as the possible ak mutation [12].
  • Noteworthy, the Lmx1b expression domain is shared by Ptx2 in posterior hypothalamic regions and by Ptx3 in the dopaminergic neurons of the ventral midbrain [18].
  • First, early events will be influenced by genes coding for transcription factors like Pax6, Pitx3, Maf or Sox [19].

Analytical, diagnostic and therapeutic context of Pitx3

  • Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation to the midbrain DA neuron phenotype in murine and human ES cell cultures [6].
  • Additionally, Pitx3 transcripts were not detected in the ak/ak mice either in the lens placode or at later developmental stages of the lens by in situ hybridization [8].
  • Furthermore, real-time PCR analyses of in vitro differentiated Pitx3-expressing ES cells revealed that genes highly expressed in A9 DA neurons were up-regulated [20].


  1. Isolation of a new homeobox gene belonging to the Pitx/Rieg family: expression during lens development and mapping to the aphakia region on mouse chromosome 19. Semina, E.V., Reiter, R.S., Murray, J.C. Hum. Mol. Genet. (1997) [Pubmed]
  2. 3,4-dihydroxyphenylalanine reverses the motor deficits in Pitx3-deficient aphakia mice: behavioral characterization of a novel genetic model of Parkinson's disease. Hwang, D.Y., Fleming, S.M., Ardayfio, P., Moran-Gates, T., Kim, H., Tarazi, F.I., Chesselet, M.F., Kim, K.S. J. Neurosci. (2005) [Pubmed]
  3. Expression of the members of the Ptx family of transcription factors in human pituitary adenomas. Pellegrini-Bouiller, I., Manrique, C., Gunz, G., Grino, M., Zamora, A.J., Figarella-Branger, D., Grisoli, F., Jaquet, P., Enjalbert, A. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  4. Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons. van den Munckhof, P., Luk, K.C., Ste-Marie, L., Montgomery, J., Blanchet, P.J., Sadikot, A.F., Drouin, J. Development (2003) [Pubmed]
  5. A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. Semina, E.V., Ferrell, R.E., Mintz-Hittner, H.A., Bitoun, P., Alward, W.L., Reiter, R.S., Funkhauser, C., Daack-Hirsch, S., Murray, J.C. Nat. Genet. (1998) [Pubmed]
  6. Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype. Martinat, C., Bacci, J.J., Leete, T., Kim, J., Vanti, W.B., Newman, A.H., Cha, J.H., Gether, U., Wang, H., Abeliovich, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Pitx3 is required for development of substantia nigra dopaminergic neurons. Nunes, I., Tovmasian, L.T., Silva, R.M., Burke, R.E., Goff, S.P. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. Deletion in the promoter region and altered expression of Pitx3 homeobox gene in aphakia mice. Semina, E.V., Murray, J.C., Reiter, R., Hrstka, R.F., Graw, J. Hum. Mol. Genet. (2000) [Pubmed]
  9. Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3. Smidt, M.P., Smits, S.M., Bouwmeester, H., Hamers, F.P., van der Linden, A.J., Hellemons, A.J., Graw, J., Burbach, J.P. Development (2004) [Pubmed]
  10. Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra and identifies a subgroup of mesencephalic dopaminergic progenitor neurons during mouse development. Maxwell, S.L., Ho, H.Y., Kuehner, E., Zhao, S., Li, M. Dev. Biol. (2005) [Pubmed]
  11. Pitx3 activates mouse tyrosine hydroxylase promoter via a high-affinity binding site. Lebel, M., Gauthier, Y., Moreau, A., Drouin, J. J. Neurochem. (2001) [Pubmed]
  12. A double-deletion mutation in the Pitx3 gene causes arrested lens development in aphakia mice. Rieger, D.K., Reichenberger, E., McLean, W., Sidow, A., Olsen, B.R. Genomics (2001) [Pubmed]
  13. Neural precursors derived from embryonic stem cells, but not those from fetal ventral mesencephalon, maintain the potential to differentiate into dopaminergic neurons after expansion in vitro. Chung, S., Shin, B.S., Hwang, M., Lardaro, T., Kang, U.J., Isacson, O., Kim, K.S. Stem Cells (2006) [Pubmed]
  14. Pitx3 deficiency in mice affects cholinergic modulation of GABAergic synapses in the nucleus accumbens. de Rover, M., Lodder, J.C., Smidt, M.P., Brussaard, A.B. J. Neurophysiol. (2006) [Pubmed]
  15. Generation of embryonic stem cells and transgenic mice expressing green fluorescence protein in midbrain dopaminergic neurons. Zhao, S., Maxwell, S., Jimenez-Beristain, A., Vives, J., Kuehner, E., Zhao, J., O'Brien, C., de Felipe, C., Semina, E., Li, M. Eur. J. Neurosci. (2004) [Pubmed]
  16. Induction of tyrosine hydroxylase expression by the transcription factor Pitx3. Messmer, K., Remington, M.P., Skidmore, F., Fishman, P.S. Int. J. Dev. Neurosci. (2007) [Pubmed]
  17. Cig30 and Pitx3 genes are arranged in a partially overlapping tail-to-tail array resulting in complementary transcripts. Tvrdik, P., Asadi, A., Kozak, L.P., Nuglozeh, E., Parente, F., Nedergaard, J., Jacobsson, A. J. Biol. Chem. (1999) [Pubmed]
  18. CNS expression pattern of Lmx1b and coexpression with ptx genes suggest functional cooperativity in the development of forebrain motor control systems. Asbreuk, C.H., Vogelaar, C.F., Hellemons, A., Smidt, M.P., Burbach, J.P. Mol. Cell. Neurosci. (2002) [Pubmed]
  19. Congenital hereditary cataracts. Graw, J. Int. J. Dev. Biol. (2004) [Pubmed]
  20. The homeodomain transcription factor Pitx3 facilitates differentiation of mouse embryonic stem cells into AHD2-expressing dopaminergic neurons. Chung, S., Hedlund, E., Hwang, M., Kim, D.W., Shin, B.S., Hwang, D.Y., Jung Kang, U., Isacson, O., Kim, K.S. Mol. Cell. Neurosci. (2005) [Pubmed]
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