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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Mesencephalon


Psychiatry related information on Mesencephalon


High impact information on Mesencephalon

  • Identification of intrinsic determinants of midbrain dopamine neurons [11].
  • These findings confirm the hypothesis that CFEOM2 results from the abnormal development of nIII/nIV (ref. 7) and emphasize a critical role for ARIX in the development of these midbrain motor nuclei [12].
  • We also show that, consistent with results obtained using other methods, uncaging eng2a (which encodes the transcription factor Engrailed2a) in the head region during early development causes a severe reduction in the size of the eye and enhanced development of the midbrain and the midbrain-hindbrain boundary at the expense of the forebrain [13].
  • Pax5 has an important role in B-cell and midbrain development [14].
  • Analysis of embryos carrying different combinations of these alleles revealed requirements for Fgf8 gene function during gastrulation, as well as cardiac, craniofacial, forebrain, midbrain and cerebellar development [15].

Chemical compound and disease context of Mesencephalon


Biological context of Mesencephalon


Anatomical context of Mesencephalon

  • Anterior midbrain crest cells in the homozygous rSey embryos reached the eye rudiments but did not migrate any further to the nasal rudiments, suggesting that the Pax-6 gene is involved in conducting migration of neural crest cells from the anterior midbrain [25].
  • These findings show that the caudal limit of Otx2 expression is sufficient for positioning the isthmic organizer and encoding caudal midbrain fate within the mid/hindbrain domain [23].
  • Midbrain development induced by FGF8 in the chick embryo [26].
  • During embryogenesis, the BSAP gene is transiently expressed in the mesencephalon and spinal cord with a spatial and temporal expression pattern that is distinct from that of other Pax genes in the developing central nervous system (CNS) [27].
  • At clinically relevant doses, selective serotonin (5-HT) reuptake inhibitors (SSRIs) and MAO inhibitors (MAOIs) increase the extracellular concentration of 5-HT in the midbrain raphé nuclei, thereby activating inhibitory somatodendritic 5-HT1A autoreceptors [28].

Associations of Mesencephalon with chemical compounds

  • In the midbrain, however, D1 receptors are selectively localized to the terminals of GABA (gamma-aminobutyric acid)-containing afferents [29].
  • In ventral midbrain dopamine neurons, activation of metabotropic glutamate receptors (mGluR1) mobilized calcium from caffeine/ryanodine-sensitive stores and increased an apamin-sensitive potassium conductance [30].
  • Nicotine activates and desensitizes midbrain dopamine neurons [31].
  • Midbrain dopamine neurons normally help to shape behaviour by reinforcing biologically rewarding events, but addictive drugs such as cocaine can inappropriately exert a reinforcing influence by acting upon the mesolimbic dopamine system [31].
  • Androgen-sensitive midbrain sites and visual attention in chicks [32].

Gene context of Mesencephalon

  • By examining embryonic expression of the mouse engrailed (En) genes, from 8.0 to 9.5 days postcoitum, we demonstrate that Wnt-1 primarily regulates midbrain development [33].
  • In rodents, glial-cell-line-derived neurotrophic factor (GDNF) stimulates an increase in midbrain dopamine levels, protects dopamine neurons from some neurotoxins, and maintains injured dopamine neurons [34].
  • Here we report that expression of En-1 in the developing midbrain of Wnt-1-null embryos is sufficient to rescue early midbrain and anterior hindbrain development [35].
  • The highly related members of the Brn-3 family have similar DNA-binding preferences and overlapping expression patterns in the sensory nervous system, midbrain and hindbrain, suggesting functional redundancy [36].
  • Injection of Six3 RNA into medaka fish embryos causes ectopic Pax6 and Rx2 expression in midbrain and cerebellum, resulting in the formation of ectopic retinal primordia [37].

Analytical, diagnostic and therapeutic context of Mesencephalon


  1. Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson's disease. Spencer, D.D., Robbins, R.J., Naftolin, F., Marek, K.L., Vollmer, T., Leranth, C., Roth, R.H., Price, L.H., Gjedde, A., Bunney, B.S. N. Engl. J. Med. (1992) [Pubmed]
  2. Epilepsy and brain abnormalities in mice lacking the Otx1 gene. Acampora, D., Mazan, S., Avantaggiato, V., Barone, P., Tuorto, F., Lallemand, Y., Brûlet, P., Simeone, A. Nat. Genet. (1996) [Pubmed]
  3. Midbrain microinfusions of prolactin increase the estrogen-dependent behavior, lordosis. Harlan, R.E., Shivers, B.D., Pfaff, D.W. Science (1983) [Pubmed]
  4. Selective blockade of hypothalamic hyperphagia and obesity in rats by serotonin-depleting midbrain lesions. Coscina, D.V., Stancer, H.C. Science (1977) [Pubmed]
  5. In vivo sequestration of Plasmodium falciparum-infected human erythrocytes: a severe combined immunodeficiency mouse model for cerebral malaria. Willimann, K., Matile, H., Weiss, N.A., Imhof, B.A. J. Exp. Med. (1995) [Pubmed]
  6. Increased midbrain gray matter in Tourette's syndrome. Garraux, G., Goldfine, A., Bohlhalter, S., Lerner, A., Hanakawa, T., Hallett, M. Ann. Neurol. (2006) [Pubmed]
  7. Bipolar disorders, dystonia, and compulsion after dysfunction of the cerebellum, dentatorubrothalamic tract, and substantia nigra. Lauterbach, E.C. Biol. Psychiatry (1996) [Pubmed]
  8. The roles of midbrain and diencephalic dopamine cell groups in the regulation of cataplexy in narcoleptic Dobermans. Okura, M., Fujiki, N., Kita, I., Honda, K., Yoshida, Y., Mignot, E., Nishino, S. Neurobiol. Dis. (2004) [Pubmed]
  9. Immunocytochemical quantification of tyrosine hydroxylase at a cellular level in the mesencephalon of control subjects and patients with Parkinson's and Alzheimer's disease. Kastner, A., Hirsch, E.C., Herrero, M.T., Javoy-Agid, F., Agid, Y. J. Neurochem. (1993) [Pubmed]
  10. Ascorbic acid increases the yield of dopaminergic neurons derived from basic fibroblast growth factor expanded mesencephalic precursors. Yan, J., Studer, L., McKay, R.D. J. Neurochem. (2001) [Pubmed]
  11. Identification of intrinsic determinants of midbrain dopamine neurons. Andersson, E., Tryggvason, U., Deng, Q., Friling, S., Alekseenko, Z., Robert, B., Perlmann, T., Ericson, J. Cell (2006) [Pubmed]
  12. Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2. Nakano, M., Yamada, K., Fain, J., Sener, E.C., Selleck, C.J., Awad, A.H., Zwaan, J., Mullaney, P.B., Bosley, T.M., Engle, E.C. Nat. Genet. (2001) [Pubmed]
  13. Photo-mediated gene activation using caged RNA/DNA in zebrafish embryos. Ando, H., Furuta, T., Tsien, R.Y., Okamoto, H. Nat. Genet. (2001) [Pubmed]
  14. Independent regulation of the two Pax5 alleles during B-cell development. Nutt, S.L., Vambrie, S., Steinlein, P., Kozmik, Z., Rolink, A., Weith, A., Busslinger, M. Nat. Genet. (1999) [Pubmed]
  15. An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination. Meyers, E.N., Lewandoski, M., Martin, G.R. Nat. Genet. (1998) [Pubmed]
  16. Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. Darios, F., Corti, O., Lücking, C.B., Hampe, C., Muriel, M.P., Abbas, N., Gu, W.J., Hirsch, E.C., Rooney, T., Ruberg, M., Brice, A. Hum. Mol. Genet. (2003) [Pubmed]
  17. AMPA and NMDA glutamate receptor subunits in midbrain dopaminergic neurons in the squirrel monkey: an immunohistochemical and in situ hybridization study. Paquet, M., Tremblay, M., Soghomonian, J.J., Smith, Y. J. Neurosci. (1997) [Pubmed]
  18. GDNF protection against 6-OHDA: time dependence and requirement for protein synthesis. Kearns, C.M., Cass, W.A., Smoot, K., Kryscio, R., Gash, D.M. J. Neurosci. (1997) [Pubmed]
  19. Progressive supranuclear palsy, computed tomography, and response to antiparkinsonian drugs. Haldeman, S., Goldman, J.W., Hyde, J., Pribram, H.F. Neurology (1981) [Pubmed]
  20. The effect of hypoxia on monoamine levels in discrete regions of aged rat brain. Roubein, I.F., Embree, L.J., Jackson, D.W., Ordway, F.S. Neurobiol. Aging (1981) [Pubmed]
  21. Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. Urbánek, P., Wang, Z.Q., Fetka, I., Wagner, E.F., Busslinger, M. Cell (1994) [Pubmed]
  22. Wnt signalling required for expansion of neural crest and CNS progenitors. Ikeya, M., Lee, S.M., Johnson, J.E., McMahon, A.P., Takada, S. Nature (1997) [Pubmed]
  23. The caudal limit of Otx2 expression positions the isthmic organizer. Broccoli, V., Boncinelli, E., Wurst, W. Nature (1999) [Pubmed]
  24. Local gene knockdown in the brain using viral-mediated RNA interference. Hommel, J.D., Sears, R.M., Georgescu, D., Simmons, D.L., DiLeone, R.J. Nat. Med. (2003) [Pubmed]
  25. A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells. Matsuo, T., Osumi-Yamashita, N., Noji, S., Ohuchi, H., Koyama, E., Myokai, F., Matsuo, N., Taniguchi, S., Doi, H., Iseki, S. Nat. Genet. (1993) [Pubmed]
  26. Midbrain development induced by FGF8 in the chick embryo. Crossley, P.H., Martinez, S., Martin, G.R. Nature (1996) [Pubmed]
  27. Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis. Adams, B., Dörfler, P., Aguzzi, A., Kozmik, Z., Urbánek, P., Maurer-Fogy, I., Busslinger, M. Genes Dev. (1992) [Pubmed]
  28. Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Artigas, F., Romero, L., de Montigny, C., Blier, P. Trends Neurosci. (1996) [Pubmed]
  29. Dopamine D1 receptors facilitate transmitter release. Cameron, D.L., Williams, J.T. Nature (1993) [Pubmed]
  30. Glutamate mediates an inhibitory postsynaptic potential in dopamine neurons. Fiorillo, C.D., Williams, J.T. Nature (1998) [Pubmed]
  31. Nicotine activates and desensitizes midbrain dopamine neurons. Pidoplichko, V.I., DeBiasi, M., Williams, J.T., Dani, J.A. Nature (1997) [Pubmed]
  32. Androgen-sensitive midbrain sites and visual attention in chicks. Meyer, C.C., Parker, D.M., Salzen, E.A. Nature (1976) [Pubmed]
  33. The midbrain-hindbrain phenotype of Wnt-1-/Wnt-1- mice results from stepwise deletion of engrailed-expressing cells by 9.5 days postcoitum. McMahon, A.P., Joyner, A.L., Bradley, A., McMahon, J.A. Cell (1992) [Pubmed]
  34. Functional recovery in parkinsonian monkeys treated with GDNF. Gash, D.M., Zhang, Z., Ovadia, A., Cass, W.A., Yi, A., Simmerman, L., Russell, D., Martin, D., Lapchak, P.A., Collins, F., Hoffer, B.J., Gerhardt, G.A. Nature (1996) [Pubmed]
  35. Engrailed-1 as a target of the Wnt-1 signalling pathway in vertebrate midbrain development. Danielian, P.S., McMahon, A.P. Nature (1996) [Pubmed]
  36. Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development. Erkman, L., McEvilly, R.J., Luo, L., Ryan, A.K., Hooshmand, F., O'Connell, S.M., Keithley, E.M., Rapaport, D.H., Ryan, A.F., Rosenfeld, M.G. Nature (1996) [Pubmed]
  37. Six3 overexpression initiates the formation of ectopic retina. Loosli, F., Winkler, S., Wittbrodt, J. Genes Dev. (1999) [Pubmed]
  38. Regional incorporation and site-specific differentiation of striatal precursors transplanted to the embryonic forebrain ventricle. Campbell, K., Olsson, M., Björklund, A. Neuron (1995) [Pubmed]
  39. TGF-beta superfamily members promote survival of midbrain dopaminergic neurons and protect them against MPP+ toxicity. Krieglstein, K., Suter-Crazzolara, C., Fischer, W.H., Unsicker, K. EMBO J. (1995) [Pubmed]
  40. Brain dopamine transporter messenger RNA and binding sites in cocaine users: a postmortem study. Little, K.Y., McLaughlin, D.P., Zhang, L., McFinton, P.R., Dalack, G.W., Cook, E.H., Cassin, B.J., Watson, S.J. Arch. Gen. Psychiatry (1998) [Pubmed]
  41. An induction gene trap for identifying a homeoprotein-regulated locus. Mainguy, G., Montesinos, M.L., Lesaffre, B., Zevnik, B., Karasawa, M., Kothary, R., Wurst, W., Prochiantz, A., Volovitch, M. Nat. Biotechnol. (2000) [Pubmed]
  42. 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]
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