Abstract
Understanding the ontogeny of A9 dopamine (DA) neurons is critical not only to determining basic developmental events that facilitate the emergence of the substantia nigra pars compacta (SNc) but also to the extraction and de novo generation of DA neurons as a potential cell therapy for Parkinson's disease. Recent research has identified a precise window for DA cell birth (differentiation) in the ventral mesencephalon (VM) as well as a number of factors that may facilitate this process. However, application of these factors in vitro has had limited success in specifying a dopaminergic cell fate from undifferentiated cells, suggesting that other cell/molecular signals may as yet remain undiscovered. To resolve this, current work seeks to identify particularly potent and novel DA neuron differentiation factors within the developing VM specifically at the moment of ontogeny. Through such (past and present) studies, a catalog of proteins that play a pivotal role in the generation of nigral DA neurons during normal CNS development has begun to emerge. In the future, it will be crucial to continue to evaluate the critical developmental window where DA neuron ontogeny occurs, not only to facilitate our potential to protect these cells from degeneration in the adult brain but also to mimic the developmental environment in a way that enhances our ability to generate these cells anew either in vitro or in vivo. Here we review our present understanding of factors that are thought to be involved in the emergence of the A9 dopamine neuron group from the ventral mesencephalon.
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References
Abbott A (2007) Neuroscience: the molecular wake-up call. Nature 447(7143):368–370
Adams B, Dorfler P, Aguzzi A, Kozmik Z, Urbanek P, Maurer-Fogy I, Busslinger M (1992) Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis. Genes Dev 6(9):1589–1607
Adams KA, Maida JM, Golden JA, Riddle RD (2000) The transcription factor Lmx1b maintains Wnt1 expression within the isthmic organizer. Development 127(9):1857–1867
Alberi L, Sgado P, Simon HH (2004) Engrailed genes are cell-autonomously required to prevent apoptosis in mesencephalic dopaminergic neurons. Development 131(13):3229–3236
Altman J, Bayer SA (1981) Development of the brain stem in the rat V. Thymidine-radiographic study of the time of origin of neurons in the midbrain tegmentum. J Comp Neurol 198(4):677–716
Andersson E, Jensen JB, Parmar M, Guillemot F, Bjorklund A (2006a) Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2. Development 133(3): 507–516
Andersson E, Tryggvason U, Deng Q, Friling S, Alekseenko Z, Robert B, Perlmann T, Ericson J (2006b) Identification of intrinsic determinants of midbrain dopamine neurons. Cell 124(2):393–405
Andersson EKI, Irvin DK, Ahlsi÷ J, Parmar M (2007) Ngn2 and Nurr1 act in synergy to induce midbrain dopaminergic neurons from expanded neural stem and progenitor cells. Exp Cell Res 313(6):1172–1180
Ang SL, Wierda A, Wong D, Stevens KA, Cascio S, Rossant J, Zaret KS (1993) The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development 119(4):1301–1315
Anthony TE, Klein C, Fishell G, Heintz N (2004) Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron 41(6):881–890
Anthony TE, Mason HA, Gridley T, Fishell G, Heintz N (2005) Brain lipid-binding protein is a direct target of Notch signaling in radial glial cells. Genes Dev 19(9):1028–1033
Arenas E (2005) Engineering a dopaminergic phenotype in stem/precursor cells: role of Nurr1, glia-derived signals, and Wnts. Ann NY Acad Sci 1049:51–66
Asano M, Gruss P (1992) Pax-5 is expressed at the midbrain-hindbrain boundary during mouse development. Mech Dev 39(1–2):29–39
Backman C, Perlmann T, Wallen A, Hoffer BJ, Morales M (1999) A selective group of dopaminergic neurons express Nurr1 in the adult mouse brain. Brain Res 851(1–2):125–132
Baffi JS, Palkovits M, Castillo SO, Mezey E, Nikodem VM (1999) Differential expression of tyrosine hydroxylase in catecholaminergic neurons of neonatal wild-type and Nurr1-deficient mice. Neuroscience 93(2):631–642
Baker JC, Beddington RS, Harland RM (1999) Wnt signaling in Xenopus embryos inhibits bmp4 expression and activates neural development. Genes Dev 13(23):3149–3159
Bjorklund A, Stenevi U (1979) Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res 177(3):555–560
Bjorklund A, Stenevi U (1971) Growth of central catecholamine neurones into smooth muscle grafts in the rat mesencephalon. Brain Res 31(1):1–20
Bjorklund LM, Sanchez-Pernaute R, Chung S, Andersson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA 99(4):2344–2349
Blaess S, Corrales JD, Joyner AL (2006) Sonic hedgehog regulates Gli activator and repressor functions with spatial and temporal precision in the mid/hindbrain region. Development 133(9):1799–1809
Bouchard M, Grote D, Craven SE, Sun Q, Steinlein P, Busslinger M (2005) Identification of Pax2-regulated genes by expression profiling of the mid-hindbrain organizer region. Development 132(11):2633–2643
Briscoe J, Pierani A, Jessell TM, Ericson J (2000) A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell 101(4):435–445
Broccoli V, Boncinelli E, Wurst W (1999) The caudal limit of Otx2 expression positions the isthmic organizer. Nature 401(6749):164–168
Brundin P, Karlsson J, Emgard M, Schierle GS, Hansson O, Petersen A, Castilho RF (2000) Improving the survival of grafted dopaminergic neurons: a review over current approaches. Cell Transplant 9(2):179–195
Bylund M, Andersson E, Novitch BG, Muhr J (2003) Vertebrate neurogenesis is counteracted by Sox1–3 activity. Nat Neurosci 6(11):1162–1168
Canning CA, Lee L, Irving C, Mason I, Jones CM (2007) Sustained interactive Wnt and FGF signaling is required to maintain isthmic identity. Dev Biol 305(1):276–286
Carlsson A, Lindqvist M, Magnusson T (1957) 3, 4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180(4596):1200
Carvey PM, Ling ZD, Sortwell CE, Pitzer MR, McGuire SO, Storch A, Collier TJ (2001) A clonal line of mesencephalic progenitor cells converted to dopamine neurons by hematopoietic cytokines: a source of cells for transplantation in Parkinson's disease. Exp Neurol 171(1):98–108
Castelo-Branco G, Wagner J, Rodriguez FJ, Kele J, Sousa K, Rawal N, Pasolli HA, Fuchs E, Kitajewski J, Arenas E (2003) Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Proc Natl Acad Sci USA 100(22): 12747–12752
Castelo-Branco G, Sousa KM, Bryja V, Pinto L, Wagner J, Arenas E (2006) Ventral midbrain glia express region-specific transcription factors and regulate dopaminergic neurogenesis through Wnt-5a secretion. Mol Cell Neurosci 31(2):251–262
Castro DS, Hermanson E, Joseph B, Wallen A, Aarnisalo P, Heller A, Perlmann T (2001) Induction of cell cycle arrest and morphological differentiation by nurr1 and retinoids in dopamine MN9D cells. J Biol Chem 276(46):43277–43284
Clancy B, Finlay BL, Darlington RB, Anand KJ (2007) Extrapolating brain development from experimental species to humans. Neurotoxicology 28(5):931–937
Correia AS, Anisimov SV, Li JY, Brundin P (2005) Stem cell-based therapy for Parkinson's disease. Ann Med 37(7):487–498
Correia SF, Anisomov SV, Roybon L, Li JY, Brundin P (2007) Fibroblast growth factor-20 increases the yield of midbrain dopaminergic neurons derived from human embryonic stem cells. Front Neuroanat 1:1–9
Crossley PH, Martinez S, Martin GR (1996) Midbrain development induced by FGF8 in the chick embryo. Nature 380(6569):66–68
Danielian PS, McMahon AP (1996) Engrailed-1 as a target of the Wnt-1 signalling pathway in vertebrate midbrain development. Nature 383(6598):332–334
Das GD, Altman J (1971) Transplanted precursors of nerve cells: their fate in the cerebellums of young rats. Science 173(997):637–638
Das GD, Hallas BH, Das KG (1979) Transplantation of neural tissues in the brains of laboratory mammals: technical details and comments. Experientia 35(2):143–153
Davis CA, Joyner AL (1988) Expression patterns of the homeo box-containing genes En-1 and En-2 and the proto-oncogene int-1 diverge during mouse development. Genes Dev 2(12B):1736–1744
Engele J, Schilling K (1996) Growth factor-induced c-fos expression defines distinct subsets of midbrain dopaminergic neurons. Neuroscience 73(2):397–406
Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292(5819):154–156
Farkas LM, Dunker N, Roussa E, Unsicker K, Krieglstein K (2003) Transforming growth factor-beta(s) are essential for the development of midbrain dopaminergic neurons in vitro and in vivo. J Neurosci 23(12):5178–5186
Ferri ALM, Lin W, Mavromatakis YE, Wang JC, Sasaki H, Whitsett JA, Ang SL (2007) Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner. Development 134(15):2761–2769
Flanders KC, Ludecke G, Engels S, Cissel DS, Roberts Ab, Kondaiah P, Lafyatis R, Sporn MB, Unsicker K (1991) Localization and actions of transforming growth factor-beta s in the embryonic nervous system. Development 113(1):183–191
Fogel JL, Chiang C, Huang X, Agarwala S (2008) Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signaling. Dev Dyn 237(5):1359–1372
Fuccillo M, Joyner AL, Fishell G (2006) Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate neural development. Nat Rev Neurosci 7(10):772–783
Gates MA, Coupe VM, Torres EM, Fricker-Gates RA, Dunnett SB (2004) Spatially and temporally restricted chemoattractive and chemorepulsive cues direct the formation of the nigro-striatal circuit. Eur J Neurosci 19(4):831–844
Gates MA, Torres EM, White A, Fricker-Gates RA, Dunnett SB (2006) Re-examining the ontogeny of substantia nigra dopamine neurons. Eur J Neurosci 23(5):1384–1390
Gemel J, Gorry M, Ehrlich GD, MacArthur CA (1996) Structure and sequence of human FGF8. Genomics 35(1):253–257
Goetz CG (1986) Charcot on Parkinson's disease. Mov Disord 1(1):27–32
Grothe C, Timmer M, Scholz T, Winkler C, Nikkhah G, Claus P, Itoh N, Arenas E (2004) Fibroblast growth factor-20 promotes the differentiation of Nurr1-overexpressing neural stem cells into tyrosine hydroxylase-positive neurons. Neurobiol Dis 17(2):163–170
Hanaway J, McConnell JA, Netsky MG (1971) Histogenesis of the substantia nigra, ventral tegmental area of Tsai and interpeduncular nucleus: an autoradiographic study of the mesencephalon in the rat. J Comp Neurol 142(1):59–73
Hanks M, Wurst W, nson-Cartwright L, Auerbach AB, Joyner AL (1995) Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2. Science 269(5224):679–682
Hatten ME (1985) Neuronal regulation of astroglial morphology and proliferation in vitro. J Cell Biol 100(2):384–396
Heikinheimo M, Lawshθ A, Shackleford GM, Wilson DB, MacArthur CA (1994) Fgf-8 expression in the post-gastrulation mouse suggests roles in the development of the face, limbs and central nervous system. Mech Dev 48(2):129–138
Henrich-Noack P, Prehn JH, Krieglstein J (1994) Neuroprotective effects of TGF-beta 1. J Neural Transm Suppl 43:33–45
Hermanson E, Joseph B, Castro D, Lindqvist E, Aarnisalo P, Wallen A, Benoit G, Hengerer B, Olson L, Perlmann T (2003) Nurr1 regulates dopamine synthesis and storage in MN9D dopamine cells. Exp Cell Res 288(2):324–334
Hirabayashi Y, Itoh Y, Tabata H, Nakajima K, Akiyama T, Masuyama N, Gotoh Y (2004) The Wnt/beta-catenin pathway directs neuronal differentiation of cortical neural precursor cells. Development 131(12):2791–2801
Hornykiewicz O (2008) Basic research on dopamine in Parkinson's disease and the discovery of the nigrostriatal dopamine pathway: the view of an eyewitness. Neurodegener Dis 5(3–4):114–117
Hwang DY, Ardayfio P, Kang UJ, Semina EV, Kim KS (2003) Selective loss of dopaminergic neurons in the substantia nigra of Pitx3-deficient aphakia mice. Brain Res Mol Brain Res 114(2): 123–131
Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350(6315):230–232
Hynes M, Stone DM, Dowd M, Pitts-Meek S, Goddard A, Gurney A, Rosenthal A (1997) Control of cell pattern in the neural tube by the zinc finger transcription factor and oncogene Gli-1. Neuron 19(1):15–26
Hynes M, Porter JA, Chiang C, Chang D, Tessier-Lavigne M, Beachy PA, Rosenthal A (1995) Induction of midbrain dopaminergic neurons by Sonic hedgehog. Neuron 15(1):35–44
Jessell TM (2000) Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev Genet 1(1):20–29
Kele J, Simplicio N, Ferri ALM, Mira H, Guillemot F, Arenas E, Ang SL (2006) Neurogenin 2 is required for the development of ventral midbrain dopaminergic neurons. Development 133(3):495–505
Kim JH, Auerbach JM, Rodriguez-Gomez JA, Velasco I, Gavin D, Lumelsky N, Lee SH, Nguyen J, Sanchez-Pernaute R, Bankiewicz K, McKay R (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 418(6893):50–56
Kitagawa H, Ray WJ, Glantschnig H, Nantermet PV, Yu Y, Leu CT, Harada S, Kato S, Freedman LP (2007) A regulatory circuit mediating convergence between Nurr1 transcriptional regulation and Wnt signaling. Mol Cell Biol 27(21):7486–7496
Krauss S, Maden M, Holder N, Wilson SW (1992) Zebrafish pax[b] is involved in the formation of the midbrain-hindbrain boundary. Nature 360(6399):87–89
Kurtz A, Zimmer A, Schnutgen F, Bruning G, Spener F, Muller T (1994) The expression pattern of a novel gene encoding brain-fatty acid binding protein correlates with neuronal and glial cell development. Development 120(9):2637–2649
Lauder JM, Bloom FE (1974) Ontogeny of monoamine neurons in the locus coeruleus Raphe nuclei and substantia nigra of the rat. I. Cell differentiation. J Comp Neurol 155(4):469–481
Le W, Conneely OM, Zou L, He Y, Saucedo-Cardenas O, Jankovic J, Mosier DR, Appel SH (1999) Selective agenesis of mesencephalic dopaminergic neurons in Nurr1-deficient mice. Exp Neurol 159(2):451–458
Lee SM, Danielian PS, Fritzsch B, McMahon AP (1997) Evidence that FGF8 signalling from the midbrain-hindbrain junction regulates growth and polarity in the developing midbrain. Development 124(5):959–969
LEES AJ (1986) L-Dopa treatment and Parkinson's disease. QJM 59(3):535–547
Li Song D, Joyner AL (2000) Two Pax2/5/8-binding sites in Engrailed2 are required for proper initiation of endogenous mid-hindbrain expression. Mech Dev 90(2):155–165
Liu A, Joyner AL (2001) EN and GBX2 play essential roles downstream of FGF8 in patterning the mouse mid/hindbrain region. Development 128(2):181–191
Liu A, Losos K, Joyner AL (1999) FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate. Development 126(21):4827–4838
Louis ED (1997) The shaking palsy, the first forty-five years: a journey through the British literature. Mov Disord 12(6):1068–1072
Lyuksyutova AI, Lu CC, Milanesio N, King LA, Guo N, Wang Y, Nathans J, Tessier-Lavigne M, Zou Y (2003) Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science 302(5652):1984–1988
Marin F, Herrero MT, Vyas S, Puelles L (2005) Ontogeny of tyrosine hydroxylase mRNA expression in mid- and forebrain: neuromeric pattern and novel positive regions. Dev Dyn 234(3):709–717
Marti J, Wills KV, Ghetti B, Bayer SA (2002) A combined immunohistochemical and autoradiographic method to detect midbrain dopaminergic neurons and determine their time of origin. Brain Res Brain Res Protoc 9(3):197–205
Martinat C, Bacci JJ, Leete T, Kim J, Vanti WB, Newman AH, Cha JH, Gether U, Wang H, Abeliovich A (2006) Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype. Proc Natl Acad Sci USA 103(8):2874–2879
Maxwell SL, Ho HY, Kuehner E, Zhao S, Li M (2005) Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra and identifies a subgroup of mesencephalic dopaminergic progenitor neurons during mouse development. Dev Biol 282(2):467–479
McMahon AP, Joyner AL, Bradley A, McMahon JA (1992) The midbrain-hindbrain phenotype of Wnt-1-/Wnt-1- mice results from stepwise deletion of engrailed-expressing cells by 9.5 days postcoitum. Cell 69(4):581–595
Millet S, Campbell K, Epstein DJ, Losos K, Harris E, Joyner AL (1999) A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer. Nature 401(6749):161–164
Muhr J, Andersson E, Persson M, Jessell TM, Ericson J (2001) Groucho-mediated transcriptional repression establishes progenitor cell pattern and neuronal fate in the ventral neural tube. Cell 104(6):861–873
Neuhoff H, Neu A, Liss B, Roeper J (2002) I(h) channels contribute to the different functional properties of identified dopaminergic subpopulations in the midbrain. J Neurosci 22(4):1290–1302
Nunes I, Tovmasian LT, Silva RM, Burke RE, Goff SP (2003) Pitx3 is required for development of substantia nigra dopaminergic neurons. Proc Natl Acad Sci USA 100(7):4245–4250
O'Hara FP, Beck E, Barr LK, Wong LL, Kessler DS, Riddle RD (2005) Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer. Development 132(14):3163–3173
O'Malley EK, Sieber BA, Black IB, Dreyfus CF (1992) Mesencephalic type I astrocytes mediate the survival of substantia nigra dopaminergic neurons in culture. Brain Res 582(1):65–70
Ohmachi S, Mikami T, Konishi M, Miyake A, Itoh N (2003) Preferential neurotrophic activity of fibroblast growth factor-20 for dopaminergic neurons through fibroblast growth factor receptor-1c. J Neurosci Res 72(4):436–443
Ohmachi S, Watanabe Y, Mikami T, Kusu N, Ibi T, Akaike A, Itoh N (2000) FGF-20, a novel neurotrophic factor, preferentially expressed in the substantia nigra pars compacta of rat brain. Biochem Biophys Res Commun 277(2):355–360
Park CH, Kang JS, Yoon EH, Shim JW, Suh-Kim H, Lee SH (2008) Proneural bHLH neurogenin 2 differentially regulates Nurr1-induced dopamine neuron differentiation in rat and mouse neural precursor cells in vitro. FEBS Lett 582(5):537–542
Parkinson J (1817) An essay on the shaking palsy. Sherwood, Neely, and Jones, London
Parr BA, Shea MJ, Vassileva G, McMahon AP (1993) Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. Development 119(1):247–261
Paul G, Li JY, Brundin P (2002) Stem cells: hype or hope? Drug Discov Today 7(5):295–302
Petrova P, Raibekas A, Pevsner J, Vigo N, Anafi M, Moore MK, Peaire AE, Shridhar V, Smith DI, Kelly J, Durocher Y, Commissiong JW (2003) MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons. J Mol Neurosci 20(2):173–188
Pevny L, Placzek M (2005) SOX genes and neural progenitor identity. Curr Opin Neurobiol 15(1):7–13
Pierani A, Brenner-Morton S, Chiang C, Jessell TM (1999) A sonic hedgehog-independent, retinoid-activated pathway of neurogenesis in the ventral spinal cord. Cell 97(7):903–915
Poulsen KT, Armanini MP, Klein RD, Hynes MA, Phillips HS, Rosenthal A (1994) TGF beta 2 and TGF beta 3 are potent survival factors for midbrain dopaminergic neurons. Neuron 13(5):1245–1252
Prakash N, Brodski C, Naserke T, Puelles E, Gogoi R, Hall A, Panhuysen M, Echevarria D, Sussel L, Weisenhorn DM, Martinez S, Arenas E, Simeone A, Wurst W (2006) A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo. Development 133(1):89–98
Prakash N, Wurst W (2007) A Wnt signal regulates stem cell fate and differentiation in vivo. Neurodegener Dis 4(4):333–338
Puelles E, Annino A, Tuorto F, Usiello A, Acampora D, Czerny T, Brodski C, Ang SL, Wurst W, Simeone A (2004) Otx2 regulates the extent, identity and fate of neuronal progenitor domains in the ventral midbrain. Development 131(9):2037–2048
Puelles L, Rubenstein JL (2003) Forebrain gene expression domains and the evolving prosomeric model. Trends Neurosci 26(9):469–476
Puelles L, Verney C (1998) Early neuromeric distribution of tyrosine-hydroxylase-immunoreactive neurons in human embryos. J Comp Neurol 394(3):283–308
Puschel AW, Westerfield M, Dressler GR (1992) Comparative analysis of Pax-2 protein distributions during neurulation in mice and zebrafish. Mech Dev 38(3):197–208
Reynolds BA, Tetzlaff W, Weiss S (1992) A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci 12(11):4565–4574
Roussa E, Farkas LM, Krieglstein K (2004) TGF-beta promotes survival on mesencephalic dopaminergic neurons in cooperation with Shh and FGF-8. Neurobiol Dis 16(2):300–310
Roussa E, Krieglstein K (2004) Induction and specification of midbrain dopaminergic cells: focus on SHH, FGF8, and TGF-beta. Cell Tissue Res 318(1):23–33
Roussa E, Wiehle M, Dunker N, Becker-Katins S, Oehlke O, Krieglstein K (2006) 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 24(9):2120–2129
Rowitch DH, McMahon AP (1995) Pax-2 expression in the murine neural plate precedes and encompasses the expression domains of Wnt-1 and En-1. Mech Dev 52(1):3–8
Roybon L, Hjalt T, Christophersen NS, Li JY, Brundin P (2008) Effects on differentiation of embryonic ventral midbrain progenitors by Lmx1a, Msx1, Ngn2, and Pitx3. J Neurosci 28(14): 3644–3656
Saarimaki-Vire J, Peltopuro P, Lahti L, Naserke T, Blak AA, Vogt Weisenhorn DM, Yu K, Ornitz DM, Wurst W, Partanen J (2007) Fibroblast growth factor receptors cooperate to regulate neural progenitor properties in the developing midbrain and hindbrain. J Neurosci 27(32):8581–8592
Sacchetti P, Carpentier R, Segard P, Olive-Cren C, Lefebvre P (2006) Multiple signaling pathways regulate the transcriptional activity of the orphan nuclear receptor NURR1. Nucleic Acids Res 34(19):5515–5527
Sacchetti P, Mitchell TR, Granneman JG, Bannon MJ (2001) Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism. J Neurochem 76(5):1565–1572
Sakurada K, Ohshima-Sakurada M, Palmer TD, Gage FH (1999) Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain. Development 126(18):4017–4026
Saucedo-Cardenas O, Quintana-Hau JD, Le WD, Smidt MP, Cox JJ, De MF, Burbach JP, Conneely OM (1998) Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc Natl Acad Sci USA 95(7):4013–4018
Schwarz M, varez-Bolado G, Urbanek P, Busslinger M, Gruss P (1997a) Conserved biological function between Pax-2 and Pax-5 in midbrain and cerebellum development: evidence from targeted mutations. Proc Natl Acad Sci USA 94(26):14518–14523
Schwarz M, Varez-Bolado G, Urbanek P, Busslinger M, Gruss P (1997b) onserved biological function between Pax-2 and Pax-5 in midbrain and cerebellum development: evidence from targetedémutations. Proc Natl Acad Sci USA 94(26):14518–14523
Simon HH, Saueressig H, Wurst W, Goulding MD, O'Leary DD (2001) Fate of midbrain dopaminergic neurons controlled by the engrailed genes. J Neurosci 21(9):3126–3134
Sinclair SR, Fawcett JW, Dunnett SB (1999) Dopamine cells in nigral grafts differentiate prior to implantation. Eur J Neurosci 11(12):4341–4348
Smidt MP, Burbach JP (2007) How to make a mesodiencephalic dopaminergic neuron. Nat Rev Neurosci 8(1):21–32
Smidt MP, Smits SM, Bouwmeester H, Hamers FP, van der Linden AJ, Hellemons AJ, Graw J, Burbach JP (2004) Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3. Development 131(5):1145–1155
Smidt MP, Smits SM, Burbach JP (2003) Molecular mechanisms underlying midbrain dopamine neuron development and function. Eur J Pharmacol 480(1–3):75–88
Smidt MP, Asbreuk CHJ, Cox JJ, Chen H, Johnson RL, Burbach JP (2000) A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b. Nat Neurosci 3(4):337–341
Smidt MP, Van Schaick HSáA, Lanctot C, Tremblay JJ, Cox JJ, Van der Kleij AA, Wolterink G, Drouin J, Burbach JP (1997) A homeodomain gene Ptx3 has highly restricted brain expression in mesencephalic dopaminergicáneurons USA. Proc Natl Acad Sci USA 94(24):13305–13310
Smits SM, Burbach JP, Smidt MP (2006) Developmental origin and fate of meso-diencephalic dopamine neurons. Prog Neurobiol 78(1):1–16
Sousa KM, Mira H, Hall AC, Jansson-Sjostrand L, Kusakabe M, Arenas E (2007) Microarray analyses support a role for nurr1 in resistance to oxidative stress and neuronal differentiation in neural stem cells. Stem Cells 25(2):511–519
Thompson L, Barraud P, Andersson E, Kirik D, Bjorklund A (2005) Identification of dopaminergic neurons of nigral and ventral tegmental area subtypes in grafts of fetal ventral mesencephalon based on cell morphology, protein expression, and efferent projections. J Neurosci 25(27):6467–6477
Thompson LH, Andersson E, Jensen JB, Barraud P, Guillemot F, Parmar M, Bj÷rklund A (2006) Neurogenin2 identifies a transplantable dopamine neuron precursor in the developing ventral mesencephalon. Exp Neurol 198(1):183–198
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147
Torres EM, Monville C, Gates MA, Bagga V, Dunnett SB (2007) Improved survival of young donor age dopamine grafts in a rat model of Parkinson's disease. Neuroscience 146(4):1606–1617
Trokovic R, Jukkola T, Saarimaki J, Peltopuro P, Naserke T, Weisenhorn DM, Trokovic N, Wurst W, Partanen J (2005) Fgfr1-dependent boundary cells between developing mid- and hindbrain. Dev Biol 278(2):428–439
Unsicker K, Krieglstein K (2002) TGF-betas and their roles in the regulation of neuron survival. Adv Exp Med Biol 513:353–374
Unsicker K, Meier C, Krieglstein K, Sartor BM, Flanders KC (1996) Expression, localization, and function of transforming growth factor-beta s in embryonic chick spinal cord, hindbrain, and dorsal root ganglia. J Neurobiol 29(2):262–276
Urbanek P, Wang ZQ, Fetka I, Wagner EF, Busslinger M (1994) Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. Cell 79(5):901–912
Urbanek P, Fetka I, Meisler MH, Busslinger M (1997) Cooperation of Pax2 and Pax5 in midbrain and cerebellumádevelopment. Proc Natl Acad Sci USA 94(11):5703–5708
Vernay B, Koch M, Vaccarino F, Briscoe J, Simeone A, Kageyama R, Ang SL (2005) Otx2 regulates subtype specification and neurogenesis in the midbrain. J Neurosci 25(19):4856–4867
Verney C, Zecevic N, Ezan P (2001) Expression of calbindin D28K in the dopaminergic mesotelencephalic system in embryonic and fetal human brain. J Comp Neurol 429(1):45–58
Volpicelli F, Caiazzo M, Greco D, Consales C, Leone L, Perrone-Capano C, DΓÇÖAmato LC, Ud P (2007) Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain neurons in vitro. J Neurochem 102(2):441–453
von Campenhausen S, Bornschein B, Wick R, Botzel K, Sampaio C, Poewe W, Oertel W, Siebert U, Berger K, Dodel R (2005) Prevalence and incidence of Parkinson's disease in Europe. Eur Neuropsychopharmacol 15(4):473–490
Voorn P, Kalsbeek A, Jorritsma-Byham B, Groenewegen HJ (1988) The pre- and postnatal development of the dopaminergic cell groups in the ventral mesencephalon and the dopaminergic innervation of the striatum of the rat. Neuroscience 25(3):857–887
Walshe J, Mason I (2000) Expression of FGFR1, FGFR2 and FGFR3 during early neural development in the chick embryo. Mech Dev 90(1):103–110
Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, Yates JR III, Nusse R (2003) Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423(6938):448–452
Ye W, Bouchard M, Stone D, Liu X, Vella F, Lee J, Nakamura H, Ang SL, Busslinger M, Rosenthal A (2001) Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8. Nat Neurosci 4(12):1175–1181
Ye W, Shimamura K, Rubenstein JL, Hynes MA, Rosenthal A (1998) FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plate. Cell 93(5):755–766
Zetterstrom RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T (1997) Dopamine neuron agenesis in Nurr1-deficient mice. Science 276(5310):248–250
Zhang J, Pho V, Bonasera SJ, Holtzman J, Tang AT, Hellmuth J, Tang S, Janak PH, Tecott LH, Huang EJ (2007) Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons. Nat Neurosci 10(1):77–86
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Orme, R., Fricker-Gates, R., Gates, M. (2009). Ontogeny of Substantia Nigra Dopamine Neurons. In: Giovanni, G., Di Matteo, V., Esposito, E. (eds) Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra. Journal of Neural Transmission. Supplementa, vol 73. Springer, Vienna. https://doi.org/10.1007/978-3-211-92660-4_1
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