Pitx3

Summary

Gene Symbol: Pitx3
Description: paired-like homeodomain transcription factor 3
Alias: Ptx3, pituitary homeobox 3, Pituitary homeobox 3 (Homeobox protein PITX3), aphakia, homeobox protein PITX3
Species: mouse
Products:     Pitx3

Top Publications

  1. Rosemann M, Ivashkevich A, Favor J, Dalke C, Holter S, Becker L, et al. Microphthalmia, parkinsonism, and enhanced nociception in Pitx3 ( 416insG ) mice. Mamm Genome. 2010;21:13-27 pubmed publisher
    ..The mutation follows a recessive pattern of inheritance and was mapped to the region of chromosome 19 containing Pitx3. Genetic complementation tests using Pitx3 ( ak/+ ) mice confirmed eyl as a new allele of Pitx3 (Pitx3 ( eyl ))...
  2. Nunes I, Tovmasian L, Silva R, Burke R, Goff S. Pitx3 is required for development of substantia nigra dopaminergic neurons. Proc Natl Acad Sci U S A. 2003;100:4245-50 pubmed
    ..We report here that mice lacking the bicoid-related homeoprotein Pitx3 fail to develop DA neurons of the substantia nigra...
  3. Lebel M, Gauthier Y, Moreau A, Drouin J. Pitx3 activates mouse tyrosine hydroxylase promoter via a high-affinity binding site. J Neurochem. 2001;77:558-67 pubmed
    ..b>Pitx3, a homeodomain-containing transcription factor, has been cloned from neuronal tissues and, in the CNS, mouse Pitx3 ..
  4. van den Munckhof P, Gilbert F, Chamberland M, Levesque D, Drouin J. Striatal neuroadaptation and rescue of locomotor deficit by L-dopa in aphakia mice, a model of Parkinson's disease. J Neurochem. 2006;96:160-70 pubmed
    ..Pitx3 deficiency in a natural mouse mutant, the aphakia mouse, was correlated with the loss of these neurons and with a deficit in locomotor activity...
  5. Zhao S, Maxwell S, Jimenez Beristain A, Vives J, Kuehner E, Zhao J, et al. Generation of embryonic stem cells and transgenic mice expressing green fluorescence protein in midbrain dopaminergic neurons. Eur J Neurosci. 2004;19:1133-40 pubmed
    ..generated embryonic stem (ES) cells and transgenic mice with green fluorescent protein (GFP) inserted into the Pitx3 locus via homologous recombination...
  6. Peng C, Aron L, Klein R, Li M, Wurst W, Prakash N, et al. Pitx3 is a critical mediator of GDNF-induced BDNF expression in nigrostriatal dopaminergic neurons. J Neurosci. 2011;31:12802-15 pubmed publisher
    b>Pitx3 is a critical homeodomain transcription factor for the proper development and survival of mesodiencephalic dopaminergic (mdDA) neurons in mammals...
  7. Semina E, Ferrell R, Mintz Hittner H, Bitoun P, Alward W, Reiter R, et al. A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. Nat Genet. 1998;19:167-70 pubmed
    We report here the identification of a new human homeobox gene, PITX3, and its involvement in anterior segment mesenchymal dysgenesis (ASMD) and congenital cataracts in humans...
  8. Jacobs F, Veenvliet J, Almirza W, Hoekstra E, von Oerthel L, van der Linden A, et al. Retinoic acid-dependent and -independent gene-regulatory pathways of Pitx3 in meso-diencephalic dopaminergic neurons. Development. 2011;138:5213-22 pubmed publisher
    ..the combined actions of the orphan nuclear receptor Nurr1 and the paired-like homeobox transcription factor Pitx3. Whereas all mdDA neurons require Nurr1 for expression of Th and survival, dependence on Pitx3 is displayed only ..
  9. Ho H, Chang K, Nichols J, Li M. Homeodomain protein Pitx3 maintains the mitotic activity of lens epithelial cells. Mech Dev. 2009;126:18-29 pubmed publisher
    Pitx3 is a bicoid like homeobox transcription factor of which deficiency in mice is linked with the aphakia phenotype...

More Information

Publications75

  1. Nakatani T, Kumai M, Mizuhara E, Minaki Y, Ono Y. Lmx1a and Lmx1b cooperate with Foxa2 to coordinate the specification of dopaminergic neurons and control of floor plate cell differentiation in the developing mesencephalon. Dev Biol. 2010;339:101-13 pubmed publisher
  2. Prakash N, Brodski C, Naserke T, Puelles E, Gogoi R, Hall A, et al. A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo. Development. 2006;133:89-98 pubmed
    ..They also suggest the Wnt1-controlled signaling pathway as a promising target for new therapeutic strategies in the treatment of Parkinson's disease. ..
  3. Chung S, Leung A, Han B, Chang M, Moon J, Kim C, et al. Wnt1-lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differentiation synergistically with the SHH-FoxA2 pathway. Cell Stem Cell. 2009;5:646-58 pubmed publisher
    ..that the Wnt1-Lmx1a autoregulatory loop directly regulates Otx2 through the beta-catenin complex and Nurr1 and Pitx3 through Lmx1a...
  4. Hwang D, Ardayfio P, Kang U, Semina E, Kim K. Selective loss of dopaminergic neurons in the substantia nigra of Pitx3-deficient aphakia mice. Brain Res Mol Brain Res. 2003;114:123-31 pubmed
    ..restricted expression in the SNc and VTA in the brain, we hypothesize that the homeobox transcription factor Pitx3 may critically regulate the development of ventral midbrain DA neurons...
  5. Jacobs F, Smits S, Noorlander C, von Oerthel L, van der Linden A, Burbach J, et al. Retinoic acid counteracts developmental defects in the substantia nigra caused by Pitx3 deficiency. Development. 2007;134:2673-84 pubmed
    Selective neuronal loss in the substantia nigra (SNc), as described for Parkinson's disease (PD) in humans and for Pitx3 deficiency in mice, highlights the existence of neuronal subpopulations...
  6. Coulon V, L honoré A, Ouimette J, Dumontier E, van den Munckhof P, Drouin J. A muscle-specific promoter directs Pitx3 gene expression in skeletal muscle cells. J Biol Chem. 2007;282:33192-200 pubmed
    ..In agreement with exclusive use of the muscle-specific promoter in aphakia mice that are deleted of the brain promoter, the trimethyl-lysine 4 histone H3 promoter signature shifts to this ..
  7. Gage P, Suh H, Camper S. The bicoid-related Pitx gene family in development. Mamm Genome. 1999;10:197-200 pubmed
  8. van den Munckhof P, Luk K, Ste Marie L, Montgomery J, Blanchet P, Sadikot A, et al. Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons. Development. 2003;130:2535-42 pubmed
    ..We now show that only a subset of MesDA neurons express Pitx3 and that in Pitx3-deficient aphakia mice, this subset is progressively lost by apoptosis during fetal (substantia nigra, SN) and postnatal (ventral ..
  9. Di Salvio M, Di Giovannantonio L, Acampora D, Prosperi R, Omodei D, Prakash N, et al. Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP. Nat Neurosci. 2010;13:1481-8 pubmed publisher
    ..These findings indicate that Otx2 is required to specify neuron subtype identity in VTA and may antagonize vulnerability to the Parkinsonian toxin MPTP. ..
  10. Semina E, Murray J, Reiter R, Hrstka R, Graw J. Deletion in the promoter region and altered expression of Pitx3 homeobox gene in aphakia mice. Hum Mol Genet. 2000;9:1575-85 pubmed
    Mouse aphakia (ak) is a recessive phenotype that spontaneously occurs in the 129/Sv-SlJ strain and is characterized by small eyes that lack a lens...
  11. Jacobs F, van Erp S, van der Linden A, von Oerthel L, Burbach J, Smidt M. Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression. Development. 2009;136:531-40 pubmed publisher
    ..In this study, we provide evidence for extensive interplay between Nurr1 and the homeobox transcription factor Pitx3 in vivo...
  12. Brodski C, Weisenhorn D, Signore M, Sillaber I, Oesterheld M, Broccoli V, et al. Location and size of dopaminergic and serotonergic cell populations are controlled by the position of the midbrain-hindbrain organizer. J Neurosci. 2003;23:4199-207 pubmed
    ..In addition, our data suggest that the position of the MHO during embryogenesis can modulate adult locomotor activity. ..
  13. Saucedo Cardenas O, Quintana Hau J, Le W, Smidt M, Cox J, De Mayo F, et al. Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc Natl Acad Sci U S A. 1998;95:4013-8 pubmed
    ..Taken together, these data indicate that Nurr1 is essential for both survival and final differentiation of ventral mesencephalic late dopaminergic precursor neurons into a complete dopaminergic phenotype. ..
  14. Castelo Branco G, Andersson E, Minina E, Sousa K, Ribeiro D, Kokubu C, et al. Delayed dopaminergic neuron differentiation in Lrp6 mutant mice. Dev Dyn. 2010;239:211-21 pubmed publisher
    ..50% reduction in tyrosine hydroxylase-positive DA neurons and in the expression of DA markers such as Nurr1 and Pitx3, as well as a defect in midbrain morphogenesis was detected in the mutant embryos at embryonic day 11.5...
  15. Ono Y, Nakatani T, Sakamoto Y, Mizuhara E, Minaki Y, Kumai M, et al. Differences in neurogenic potential in floor plate cells along an anteroposterior location: midbrain dopaminergic neurons originate from mesencephalic floor plate cells. Development. 2007;134:3213-25 pubmed
    ..Our data provide insights into the mechanisms of specification and generation of mesDA neurons, and illustrate a useful cell replacement approach for Parkinson's disease. ..
  16. Guimera J, Weisenhorn D, Wurst W. Megane/Heslike is required for normal GABAergic differentiation in the mouse superior colliculus. Development. 2006;133:3847-57 pubmed
    ..Vertebrate h/E(spl)-related genes can no longer be regarded solely as a factors that confer generic neurogenic properties, but as key components for the subtype-neuronal identity in the mammalian CNS. ..
  17. Smits S, Burbach J, Smidt M. Developmental origin and fate of meso-diencephalic dopamine neurons. Prog Neurobiol. 2006;78:1-16 pubmed
    ..The data indicate that these specific subsets may explain the specific response of these neurons to toxins and genetic ablation. ..
  18. Smidt M, Smits S, Bouwmeester H, Hamers F, van der Linden A, Hellemons A, et al. Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3. Development. 2004;131:1145-55 pubmed
    ..5, a time when tyrosine hydroxylase (Th) gene expression is initiated. We show here that, in the Pitx3-deficient aphakia (ak) mouse mutant, the mesDA system is malformed...
  19. Kele J, Simplicio N, Ferri A, Mira H, Guillemot F, Arenas E, et al. Neurogenin 2 is required for the development of ventral midbrain dopaminergic neurons. Development. 2006;133:495-505 pubmed
    ..These results demonstrate that Ngn2 is uniquely required for the development of midbrain dopaminergic neurons. ..
  20. Smits S, Noorlander C, Kas M, Ramakers G, Smidt M. Alterations in serotonin signalling are involved in the hyperactivity of Pitx3-deficient mice. Eur J Neurosci. 2008;27:388-95 pubmed publisher
    b>Pitx3 deficiency in mice causes a dramatic loss of dopaminergic neurones located in the substantia nigra pars compacta during development...
  21. L honoré A, Coulon V, Marcil A, Lebel M, Lafrance Vanasse J, Gage P, et al. Sequential expression and redundancy of Pitx2 and Pitx3 genes during muscle development. Dev Biol. 2007;307:421-33 pubmed
    ..We now report the expression of Pitx2 and Pitx3 transcription factors throughout muscle development...
  22. Medina Martinez O, Shah R, Jamrich M. Pitx3 controls multiple aspects of lens development. Dev Dyn. 2009;238:2193-201 pubmed publisher
    ..Deletions in the promoter of this gene cause abnormal lens development in the aphakia (ak) mouse mutant, which has only rudimentary lenses...
  23. Kadkhodaei B, Ito T, Joodmardi E, Mattsson B, Rouillard C, Carta M, et al. Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons. J Neurosci. 2009;29:15923-32 pubmed publisher
  24. Ahmad N, Aslam M, Muenster D, Horsch M, Khan M, Carlsson P, et al. Pitx3 directly regulates Foxe3 during early lens development. Int J Dev Biol. 2013;57:741-51 pubmed publisher
    ..In aphakia (ak) mice, two deletions in the promoter region of Pitx3 cause abnormal lens development...
  25. Andersson E, Jensen J, Parmar M, Guillemot F, Bjorklund A. Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2. Development. 2006;133:507-16 pubmed
  26. Grimm C, Chatterjee B, Favor J, Immervoll T, Loster J, Klopp N, et al. Aphakia (ak), a mouse mutation affecting early eye development: fine mapping, consideration of candidate genes and altered Pax6 and Six3 gene expression pattern. Dev Genet. 1998;23:299-316 pubmed
    The homozygous mouse mutant aphakia (ak) has been characterized by bilaterally aphakic eyes without a pupil [Varnum DS, Stevens, LC (1968): J Hered 59:147-150]...
  27. Martinat C, Bacci J, Leete T, Kim J, Vanti W, Newman A, et al. Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype. Proc Natl Acad Sci U S A. 2006;103:2874-9 pubmed
    ..of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2...
  28. Varnum D, Stevens L. Aphakia, a new mutation in the mouse. J Hered. 1968;59:147-50 pubmed
  29. Hwang D, Fleming S, Ardayfio P, Moran Gates T, Kim H, Tarazi F, et al. 3,4-dihydroxyphenylalanine reverses the motor deficits in Pitx3-deficient aphakia mice: behavioral characterization of a novel genetic model of Parkinson's disease. J Neurosci. 2005;25:2132-7 pubmed
    ..Here, we demonstrate that Pitx3-deficient aphakia (ak) mice, which have been shown previously to exhibit a major loss of substantia nigra dopaminergic neurons, ..
  30. Smidt M, Asbreuk C, Cox J, Chen H, Johnson R, Burbach J. A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b. Nat Neurosci. 2000;3:337-41 pubmed
    ..or Nurr1, a nuclear hormone receptor, Lmx1b knockout mice failed to induce the mesDA-specific homeodomain gene Ptx3 in TH-positive neurons. Eventually, this small set of TH-positive neurons was lost during embryonic maturation...
  31. Hwang D, Hong S, Jeong J, Choi S, Kim H, Kim J, et al. Vesicular monoamine transporter 2 and dopamine transporter are molecular targets of Pitx3 in the ventral midbrain dopamine neurons. J Neurochem. 2009;111:1202-12 pubmed publisher
    ..target genes of Pitx3 by comparing gene expression profiles in mDA neurons of wild-type and Pitx3-deficient aphakia mice...
  32. Jacobs F, van der Linden A, Wang Y, von Oerthel L, Sul H, Burbach J, et al. Identification of Dlk1, Ptpru and Klhl1 as novel Nurr1 target genes in meso-diencephalic dopamine neurons. Development. 2009;136:2363-73 pubmed publisher
    ..of meso-diencephalic dopamine (mdDA) neurons and is required, together with the homeobox transcription factor Pitx3, for the expression of genes involved in dopamine metabolism...
  33. Smidt M, van Schaick H, Lanctot C, Tremblay J, Cox J, Van Der Kleij A, et al. A homeodomain gene Ptx3 has highly restricted brain expression in mesencephalic dopaminergic neurons. Proc Natl Acad Sci U S A. 1997;94:13305-10 pubmed
    ..We have identified a bicoid-related homeobox gene, Ptx3, a member of the Ptx-subfamily, that is uniquely expressed in these neurons. Its expression starting at E11...
  34. Semina E, Reiter R, Murray J. 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. Hum Mol Genet. 1997;6:2109-16 pubmed
    ..p.c. embryos. Pitx3 was mapped close to aphakia on mouse chromosome 19...
  35. Vives J, Sasajala P, Chang K, Zhao S, Li M. A mouse model for tracking nigrostriatal dopamine neuron axon growth. Genesis. 2008;46:125-31 pubmed publisher
    ..We have generated a knock-in reporter mouse line with the tau-lacZ fusion gene inserted into the Pitx3 locus via homologous recombination...
  36. Smits S, Ponnio T, Conneely O, Burbach J, Smidt M. Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic neurons. Eur J Neurosci. 2003;18:1731-8 pubmed
    ..5 and 14.5. Here we demonstrate that induction of VMAT2 and DAT specifically in mesDA neurons requires Nurr1 expression, whereas AADC expression in mesDA neurons is induced independently of Nurr1 function. ..
  37. Tang M, Miyamoto Y, Huang E. Multiple roles of beta-catenin in controlling the neurogenic niche for midbrain dopamine neurons. Development. 2009;136:2027-38 pubmed publisher
    ..They also suggest that beta-catenin-mediated signaling pathways can be targeted to promote and expand DA neurons in cell-based therapeutic strategies. ..
  38. Rieger D, Reichenberger E, McLean W, Sidow A, Olsen B. A double-deletion mutation in the Pitx3 gene causes arrested lens development in aphakia mice. Genomics. 2001;72:61-72 pubmed
    The recessive aphakia (ak) mouse mutant is characterized by bilateral microphthalmia due to a failure of lens morphogenesis...
  39. Luk K, Rymar V, van den Munckhof P, Nicolau S, Steriade C, Bifsha P, et al. The transcription factor Pitx3 is expressed selectively in midbrain dopaminergic neurons susceptible to neurodegenerative stress. J Neurochem. 2013;125:932-43 pubmed publisher
    ..Here, we identify specific mDA cell subpopulations that are consistently spared in adult Pitx3-hypomorphic (aphakia) mice, demonstrating that Pitx3 is not indiscriminately required by all mDA neurons for their survival...
  40. Thuret S, Alavian K, Gassmann M, Lloyd C, Smits S, Smidt M, et al. The neuregulin receptor, ErbB4, is not required for normal development and adult maintenance of the substantia nigra pars compacta. J Neurochem. 2004;91:1302-11 pubmed
    ..Finally, an assessment of their motor function revealed no behavioral deficits. The apparent lack of any mutant phenotype suggests the presence of a strong compensatory mechanism. ..
  41. Lennington J, Pope S, Goodheart A, Drozdowicz L, Daniels S, Salamone J, et al. Midbrain dopamine neurons associated with reward processing innervate the neurogenic subventricular zone. J Neurosci. 2011;31:13078-87 pubmed publisher
    ..However, when we examined the aphakia mouse, which is deficient in nigrostriatal neurons, we found no detrimental effect to SVZ proliferation or ..
  42. Kim S, Zhao Y, Lee J, Kim W, Gorivodsky M, Westphal H, et al. Ldb1 Is Essential for the Development of Isthmic Organizer and Midbrain Dopaminergic Neurons. Stem Cells Dev. 2016;25:986-94 pubmed publisher
  43. Lin X, Parisiadou L, Sgobio C, Liu G, Yu J, Sun L, et al. Conditional expression of Parkinson's disease-related mutant α-synuclein in the midbrain dopaminergic neurons causes progressive neurodegeneration and degradation of transcription factor nuclear receptor related 1. J Neurosci. 2012;32:9248-64 pubmed publisher
  44. Clark J, Silvaggi J, Kiselak T, Zheng K, Clore E, Dai Y, et al. Pgc-1? overexpression downregulates Pitx3 and increases susceptibility to MPTP toxicity associated with decreased Bdnf. PLoS ONE. 2012;7:e48925 pubmed publisher
    ..Reduced Th expression was associated with loss of Pitx3, a transcription factor that is critical for the development and maintenance of dopaminergic cells...
  45. Le W, Zhang L, Xie W, Li S, Dani J. Pitx3 deficiency produces decreased dopamine signaling and induces motor deficits in Pitx3(-/-) mice. Neurobiol Aging. 2015;36:3314-3320 pubmed publisher
    ..The homeobox transcription factor, Pitx3, plays a critical role in the development, function, and maintenance of midbrain DA neurons...
  46. Sgobio C, Wu J, Zheng W, Chen X, Pan J, Salinas A, et al. Aldehyde dehydrogenase 1-positive nigrostriatal dopaminergic fibers exhibit distinct projection pattern and dopamine release dynamics at mouse dorsal striatum. Sci Rep. 2017;7:5283 pubmed publisher
    ..Together, these results demonstrate distinct dopamine release characteristics of ALDH1A1-positive DA fibers, supporting a regional specific function of ALDH1A1 in regulating dopamine availability/release in striatum. ..
  47. Stuebner S, Faus Kessler T, Fischer T, Wurst W, Prakash N. Fzd3 and Fzd6 deficiency results in a severe midbrain morphogenesis defect. Dev Dyn. 2010;239:246-60 pubmed publisher
    ..Fzd3 and Fzd6 thus control proper midbrain morphogenesis by a yet unknown mechanism in the mouse. ..
  48. Andersson E, Prakash N, Cajanek L, Minina E, Bryja V, Bryjova L, et al. Wnt5a regulates ventral midbrain morphogenesis and the development of A9-A10 dopaminergic cells in vivo. PLoS ONE. 2008;3:e3517 pubmed publisher
  49. Smits S, Mathon D, Burbach J, Ramakers G, Smidt M. Molecular and cellular alterations in the Pitx3-deficient midbrain dopaminergic system. Mol Cell Neurosci. 2005;30:352-63 pubmed
    ..system in pathology, specific molecular and cellular parameters of the mDA system were studied in Pitx3-deficient Aphakia (ak) mice, which suffer from severe developmental failure of SNc mDA neurons...
  50. Pontoriero G, Deschamps P, Ashery Padan R, Wong R, Yang Y, Zavadil J, et al. Cell autonomous roles for AP-2alpha in lens vesicle separation and maintenance of the lens epithelial cell phenotype. Dev Dyn. 2008;237:602-17 pubmed publisher
    ..Expression of known regulators of lens vesicle separation, including Pax6, Pitx3, and Foxe3 was observed in the Le-AP-2alpha mutant lens demonstrating that these genes do not lie directly ..
  51. Roussa E, Wiehle M, Dünker N, Becker Katins S, Oehlke O, Krieglstein K. Transforming growth factor beta is required for differentiation of mouse mesencephalic progenitors into dopaminergic neurons in vitro and in vivo: ectopic induction in dorsal mesencephalon. Stem Cells. 2006;24:2120-9 pubmed
    ..Together, the results clearly demonstrate that TGF-beta2 and TGF-beta3 are essential signals for differentiation of midbrain progenitors toward neuronal fate and dopaminergic phenotype. ..
  52. Ardayfio P, Leung A, Park J, Hwang D, Moran Gates T, Choi Y, et al. Pitx3-deficient aphakia mice display unique behavioral responses to psychostimulant and antipsychotic drugs. Neuroscience. 2010;166:391-6 pubmed publisher
    ..Pitx3 is a transcription factor enriched in DA neurons. Aphakia (ak) mice deficient in Pitx3 show selective loss of nigrostriatal DA, while other DA pathways are relatively ..
  53. Luo J, Sun L, Lin X, Liu G, Yu J, Parisiadou L, et al. A calcineurin- and NFAT-dependent pathway is involved in ?-synuclein-induced degeneration of midbrain dopaminergic neurons. Hum Mol Genet. 2014;23:6567-74 pubmed publisher
    ..These findings demonstrate an active involvement of CN- and NFAT-mediated signalling pathway in ?-syn-mediated degeneration of mDA neurons in PD. ..
  54. Havrda M, Paolella B, Ward N, Holroyd K. Behavioral abnormalities and Parkinson's-like histological changes resulting from Id2 inactivation in mice. Dis Model Mech. 2013;6:819-27 pubmed publisher
    ..These findings document a novel role for Id2 in the maintenance of midbrain dopamine neurons. The Id2(-/-) mouse should provide unique opportunities to study the progression of neurodegenerative disorders involving the dopamine system. ..
  55. Zhang J, Pho V, Bonasera S, Holtzman J, Tang A, Hellmuth J, et al. Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons. Nat Neurosci. 2007;10:77-86 pubmed
    ..These data underscore the importance of the TGFbeta-Smad-HIPK2 pathway in the survival of DA neurons and its potential as a therapeutic target for promoting DA neuron survival during neurodegeneration. ..
  56. Lim S, Xia R, Ding Y, Won L, Ray W, Hitchcock S, et al. Enhanced histamine H2 excitation of striatal cholinergic interneurons in L-DOPA-induced dyskinesia. Neurobiol Dis. 2015;76:67-76 pubmed publisher
    ..Using two different mouse models of PD (6-hydroxydopamine lesion and Pitx3(ak/ak) mutation), we chronically treated the animals with either vehicle or l-DOPA to induce dyskinesia...
  57. Nouri N, Patel M, Joksimovic M, Poulin J, Anderegg A, Taketo M, et al. Excessive Wnt/beta-catenin signaling promotes midbrain floor plate neurogenesis, but results in vacillating dopamine progenitors. Mol Cell Neurosci. 2015;68:131-42 pubmed publisher
    ..Our findings will impact embryonic stem cell protocols that utilize Wnt pathway reagents to derive mDA neuron models and therapeutics for Parkinson's disease. ..
  58. Espadas I, Darmopil S, Vergaño Vera E, Ortiz O, Oliva I, Vicario Abejón C, et al. L-DOPA-induced increase in TH-immunoreactive striatal neurons in parkinsonian mice: insights into regulation and function. Neurobiol Dis. 2012;48:271-81 pubmed publisher
    ..Interestingly, our experiments in aphakia mice, which lack Pitx3 expression in the brain, indicate that the L-DOPA-dependent increase in the number of TH-..
  59. Fukusumi Y, Meier F, Götz S, Matheus F, Irmler M, Beckervordersandforth R, et al. Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse. J Neurosci. 2015;35:13385-401 pubmed publisher
    ..and is required for the activation and/or maintenance of LMX1A (LIM homeobox transcription factor 1α) and PITX3 (paired-like homeodomain transcription factor 3) expression in the corresponding mdDA precursor subset, without ..
  60. Gazea M, Tasouri E, Tolve M, Bosch V, Kabanova A, Gojak C, et al. Primary cilia are critical for Sonic hedgehog-mediated dopaminergic neurogenesis in the embryonic midbrain. Dev Biol. 2016;409:55-71 pubmed publisher
  61. Tvrdik P, Asadi A, Kozak L, Nuglozeh E, Parente F, Nedergaard J, et al. Cig30 and Pitx3 genes are arranged in a partially overlapping tail-to-tail array resulting in complementary transcripts. J Biol Chem. 1999;274:26387-92 pubmed
    ..It turned out to be the newly identified homeobox gene Pitx3. Interestingly, the genes are very tightly linked, so that the 3' ends of their transcripts are complementary...
  62. L honoré A, Commere P, Ouimette J, Montarras D, Drouin J, Buckingham M. Redox regulation by Pitx2 and Pitx3 is critical for fetal myogenesis. Dev Cell. 2014;29:392-405 pubmed publisher
    ..Our analysis identifies Pitx2 and Pitx3 as key regulators of the intracellular redox state preventing DNA damage as cells undergo differentiation.
  63. Simon R, Lufkin T. Postnatal lethality in mice lacking the Sax2 homeobox gene homologous to Drosophila S59/slouch: evidence for positive and negative autoregulation. Mol Cell Biol. 2003;23:9046-60 pubmed
    ..Intriguingly, our studies also demonstrated a striking autoregulation of the Sax2 gene in both positive- and negative-feedback mechanisms depending on the specific cell type expressing Sax2. ..
  64. Kameda Y, Saitoh T, Fujimura T. Hes1 regulates the number and anterior-posterior patterning of mesencephalic dopaminergic neurons at the mid/hindbrain boundary (isthmus). Dev Biol. 2011;358:91-101 pubmed publisher
    ..e., the isthmic organizer). Using mesDA neuronal markers, tyrosine hydroxylase (TH) and Pitx3, the development of mesDA neurons was studied in Hes1 null mice and compared with that in the wild type...
  65. Kouwenhoven W, Veenvliet J, van Hooft J, van der Heide L, Smidt M. Engrailed 1 shapes the dopaminergic and serotonergic landscape through proper isthmic organizer maintenance and function. Biol Open. 2016;5:279-88 pubmed publisher
    ..Our work suggests a newly-discovered role for En1: the repression of Otx2, Wnt1 and canonical Wnt-signaling in R1. Overall, our results suggest that En1 is essential for proper IsO maintenance and function. ..
  66. Zheng M, Jiao L, Tang X, Xiang X, Wan X, Yan Y, et al. Tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor orthodenticle homeobox 2 expression. FASEB J. 2017;31:3349-3358 pubmed publisher
    ..Li, X., Zhang, G., Li, Y., Jiang, B., Cai, H., Lin, X. Tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor orthodenticle homeobox 2 expression. ..