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PMID: 16388109 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

From radial glia to pyramidal-projection neuron: transcription factor cascades in cerebral cortex development.

Molecular neurobiology ·Vol. 33 ·No. 1 ·2006-02-00 ·Pages 33-50

Hevner RF

Abstract

Pyramidal-projection neurons are glutamatergic neurons that develop from progenitors in the ventricular and subventricular zones of the embryonic cortex. Recently, much has been learned about the cortical progenitor cells and the cellular and molecular mechanisms by which they produce projection neurons. We now know that radial glia are the progenitors of most or all projection neurons and that they generate neurons by two distinct mitotic sequences: direct neurogenesis to produce a single daughter neuron or indirect neurogenesis to produce two to four neurons via intermediate progenitor cells. The underlying genetic programs for proliferation and differentiation are controlled and implemented by specific transcription factors, whose interactions largely determine the cortical surface area, thickness, and neuronal subtype composition. In turn, transcription factor expression is modulated by extrinsic signals from patterning centers and adjacent cells and by intrinsic signals distributed asymmetrically within progenitors and daughter cells. Together, the new findings provide a coherent framework for understanding cortical neurogenesis.

MeSH Terms
Animals Cell Differentiation/genetics Cell Movement/genetics Cell Proliferation Cerebral Cortex/cytology,embryology,metabolism Gene Expression Regulation, Developmental/genetics Humans Neuroglia/cytology,metabolism Pyramidal Cells/cytology,metabolism Signal Transduction/genetics Stem Cells/cytology,metabolism Transcription Factors/genetics,physiology
Chemicals
Transcription Factors
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Hevner Robert F
Department of Pathology (Neuropathology), University of Washington School of Medicine, Seattle, WA, USA. rhevner@u.washington.edu
References (104)
104 references, click to expand
  1. Emx2 promotes symmetric cell divisions and a multipotential fate in precursors from the cerebral cortex.
    Mol Cell Neurosci. 2001 Nov;18(5):485-502 PMID: 11922140
  2. Diversifying neural cells through order of birth and asymmetry of division.
    Neuron. 2003 Jan 9;37(1):11-4 PMID: 12526768
  3. Neural bHLH genes control the neuronal versus glial fate decision in cortical progenitors.
    Neuron. 2001 Feb;29(2):401-13 PMID: 11239431
  4. Cortical neuron specification: it has its time and place.
    Neuron. 2005 May 5;46(3):373-6 PMID: 15882634
  5. Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex.
    Development. 2004 Nov;131(22):5639-47 PMID: 15509764
  6. The bHLH gene hes1 as a repressor of the neuronal commitment of CNS stem cells.
    J Neurosci. 2000 Jan 1;20(1):283-93 PMID: 10627606
  7. The Tlx gene regulates the timing of neurogenesis in the cortex.
    J Neurosci. 2004 Sep 22;24(38):8333-45 PMID: 15385616
  8. Generation of reelin-positive marginal zone cells from the caudomedial wall of telencephalic vesicles.
    J Neurosci. 2004 Mar 3;24(9):2286-95 PMID: 14999079
  9. Emx1 and Emx2 cooperate to regulate cortical size, lamination, neuronal differentiation, development of cortical efferents, and thalamocortical pathfinding.
    J Comp Neurol. 2003 Mar 17;457(4):345-60 PMID: 12561075
  10. Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex.
    J Neurosci. 2005 Jan 5;25(1):247-51 PMID: 15634788
  11. Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts.
    Nature. 1999 Oct 14;401(6754):670-7 PMID: 10537105
  12. Conversion of cerebral cortex into basal ganglia in Emx2(-/-) Pax6(Sey/Sey) double-mutant mice.
    Nat Neurosci. 2002 Aug;5(8):737-45 PMID: 12118260
  13. Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo.
    Neuron. 2005 Jan 20;45(2):207-21 PMID: 15664173
  14. Constructing the mammalian neocortex: the role of intrinsic factors.
    Dev Biol. 2003 May 15;257(2):221-32 PMID: 12729554
  15. Glial cells generate neurons: the role of the transcription factor Pax6.
    Nat Neurosci. 2002 Apr;5(4):308-15 PMID: 11896398
  16. Insulin-like growth factor-I accelerates the cell cycle by decreasing G1 phase length and increases cell cycle reentry in the embryonic cerebral cortex.
    J Neurosci. 2004 Nov 10;24(45):10201-10 PMID: 15537892
  17. Constructing the cerebral cortex: neurogenesis and fate determination.
    Neuron. 1995 Oct;15(4):761-8 PMID: 7576626
  18. Embryonic vertebrate central nervous system: revised terminology. The Boulder Committee.
    Anat Rec. 1970 Feb;166(2):257-61 PMID: 5414696
  19. GABA immunoreactive neurons in rat visual cortex.
    J Comp Neurol. 1987 Jul 15;261(3):388-404 PMID: 3301920
  20. Radial glia serve as neuronal progenitors in all regions of the central nervous system.
    Neuron. 2004 Mar 25;41(6):881-90 PMID: 15046721
  21. Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain.
    J Biol Chem. 2001 Aug 10;276(32):30467-74 PMID: 11399758
  22. EMX2 protein in the developing mouse brain and olfactory area.
    Mech Dev. 1998 Oct;77(2):165-72 PMID: 9831645
  23. Molecular dissection of Pax6 function: the specific roles of the paired domain and homeodomain in brain development.
    Development. 2004 Dec;131(24):6131-40 PMID: 15548580
  24. Emx1 is a marker for pyramidal neurons of the cerebral cortex.
    Cereb Cortex. 2001 Dec;11(12):1191-8 PMID: 11709490
  25. Regulation of area identity in the mammalian neocortex by Emx2 and Pax6.
    Science. 2000 Apr 14;288(5464):344-9 PMID: 10764649
  26. Developmental and evolutionary adaptations of cortical radial glia.
    Cereb Cortex. 2003 Jun;13(6):541-9 PMID: 12764027
  27. Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse.
    Nature. 1961 Nov 25;192:766-8 PMID: 17533671
  28. Radial glial cells defined and major intermediates between embryonic stem cells and CNS neurons.
    Neuron. 2005 May 5;46(3):369-72 PMID: 15882633
  29. Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells.
    Development. 2004 Jul;131(13):3133-45 PMID: 15175243
  30. Foxg1 suppresses early cortical cell fate.
    Science. 2004 Jan 2;303(5654):56-9 PMID: 14704420
  31. Pax6 is required to regulate the cell cycle and the rate of progression from symmetrical to asymmetrical division in mammalian cortical progenitors.
    Development. 2002 Jan;129(2):455-66 PMID: 11807037
  32. Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases.
    Nat Neurosci. 2004 Feb;7(2):136-44 PMID: 14703572
  33. Tbr1 regulates differentiation of the preplate and layer 6.
    Neuron. 2001 Feb;29(2):353-66 PMID: 11239428
  34. Patterns of neuronal migration in the embryonic cortex.
    Trends Neurosci. 2004 Jul;27(7):392-9 PMID: 15219738
  35. Pax6 controls radial glia differentiation in the cerebral cortex.
    Neuron. 1998 Nov;21(5):1031-44 PMID: 9856459
  36. Novel transcription factor Satb2 interacts with matrix attachment region DNA elements in a tissue-specific manner and demonstrates cell-type-dependent expression in the developing mouse CNS.
    Eur J Neurosci. 2005 Feb;21(3):658-68 PMID: 15733084
  37. Two modes of radial migration in early development of the cerebral cortex.
    Nat Neurosci. 2001 Feb;4(2):143-50 PMID: 11175874
  38. Numbers and proportions of GABA-immunoreactive neurons in different areas of monkey cerebral cortex.
    J Neurosci. 1987 May;7(5):1503-19 PMID: 3033170
  39. Asymmetric distribution of EGFR receptor during mitosis generates diverse CNS progenitor cells.
    Neuron. 2005 Mar 24;45(6):873-86 PMID: 15797549
  40. A long, remarkable journey: tangential migration in the telencephalon.
    Nat Rev Neurosci. 2001 Nov;2(11):780-90 PMID: 11715055
  41. Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells.
    EMBO J. 2004 Jun 2;23(11):2314-24 PMID: 15141162
  42. Direct and concentration-dependent regulation of the proneural gene Neurogenin2 by Pax6.
    Development. 2003 Jul;130(14 ):3269-81 PMID: 12783797
  43. Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis.
    Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3196-201 PMID: 14963232
  44. Neuronal basic helix-loop-helix proteins (NEX, neuroD, NDRF): spatiotemporal expression and targeted disruption of the NEX gene in transgenic mice.
    J Neurosci. 1998 Feb 15;18(4):1408-18 PMID: 9454850
  45. Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms.
    Cell. 2001 Feb 9;104(3):365-76 PMID: 11239394
  46. Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage.
    Development. 2000 Dec;127(24):5253-63 PMID: 11076748
  47. Foxg1 confines Cajal-Retzius neuronogenesis and hippocampal morphogenesis to the dorsomedial pallium.
    J Neurosci. 2005 Apr 27;25(17):4435-41 PMID: 15858069
  48. Cell cycle dependence of laminar determination in developing neocortex.
    Science. 1991 Oct 11;254(5029):282-5 PMID: 1925583
  49. Visualization of mitotic radial glial lineage cells in the developing rat brain by Cdc2 kinase-phosphorylated vimentin.
    Glia. 1998 Jul;23(3):191-9 PMID: 9633804
  50. Proliferative characteristics of the ependymal layer during the early development of the mouse neocortex: a pilot study based on recording the number, location and plane of cleavage of mitotic figures.
    J Anat. 1973 Oct;116(Pt 1):67-91 PMID: 4777782
  51. Emx homeogenes and mouse brain development.
    Trends Neurosci. 2000 Aug;23(8):347-52 PMID: 10906797
  52. Dynamics of Cux2 expression suggests that an early pool of SVZ precursors is fated to become upper cortical layer neurons.
    Cereb Cortex. 2004 Dec;14(12):1408-20 PMID: 15238450
  53. Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways.
    EMBO J. 2004 Jul 21;23 (14 ):2892-902 PMID: 15229646
  54. Characterization of CNS precursor subtypes and radial glia.
    Dev Biol. 2001 Jan 1;229(1):15-30 PMID: 11133151
  55. Size distribution of retrovirally marked lineages matches prediction from population measurements of cell cycle behavior.
    J Neurosci Res. 2002 Sep 15;69(6):731-44 PMID: 12205666
  56. Genesis of GABA-immunoreactive neurons in the ferret visual cortex.
    J Neurosci. 1988 Mar;8(3):920-31 PMID: 3346729
  57. Id4 regulates neural progenitor proliferation and differentiation in vivo.
    Development. 2004 Nov;131(21):5441-8 PMID: 15469968
  58. EMX2 regulates sizes and positioning of the primary sensory and motor areas in neocortex by direct specification of cortical progenitors.
    Neuron. 2004 Aug 5;43(3):359-72 PMID: 15294144
  59. Expression of neuroD/BETA2 in mitotic and postmitotic neuronal cells during the development of nervous system.
    Dev Dyn. 2000 Apr;217(4):361-7 PMID: 10767080
  60. Tlx and Pax6 co-operate genetically to establish the pallio-subpallial boundary in the embryonic mouse telencephalon.
    Development. 2003 Mar;130(6):1113-22 PMID: 12571103
  61. Basic helix-loop-helix factors in cortical development.
    Neuron. 2003 Jul 3;39(1):13-25 PMID: 12848929
  62. Mouse models of telencephalic development.
    Curr Opin Genet Dev. 2003 Aug;13(4):423-37 PMID: 12888017
  63. Early divergence and changing proportions of neuronal and glial precursor cells in the primate cerebral ventricular zone.
    Dev Biol. 1983 Apr;96(2):472-84 PMID: 6339301
  64. Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon.
    Development. 2001 Jan;128(2):193-205 PMID: 11124115
  65. Neuronal or glial progeny: regional differences in radial glia fate.
    Neuron. 2003 Mar 6;37(5):751-64 PMID: 12628166
  66. Progenitors resume generating neurons after temporary inhibition of neurogenesis by Notch activation in the mammalian cerebral cortex.
    Development. 2005 Mar;132(6):1295-304 PMID: 15750183
  67. Coexistence of neuronal and glial precursor cells in the cerebral ventricular zone of the fetal monkey: an ultrastructural immunoperoxidase analysis.
    J Neurosci. 1981 Jan;1(1):27-39 PMID: 7050307
  68. Organization and development of corticocortical associative neurons expressing the orphan nuclear receptor Nurr1.
    J Comp Neurol. 2003 Nov 10;466(2):180-96 PMID: 14528447
  69. Neurons from radial glia: the consequences of asymmetric inheritance.
    Curr Opin Neurobiol. 2003 Feb;13(1):34-41 PMID: 12593980
  70. Molecular mechanisms underlying cell fate specification in the developing telencephalon.
    Curr Opin Neurobiol. 2002 Feb;12(1):26-34 PMID: 11861161
  71. Neurons derived from radial glial cells establish radial units in neocortex.
    Nature. 2001 Feb 8;409(6821):714-20 PMID: 11217860
  72. Multipolar migration: the third mode of radial neuronal migration in the developing cerebral cortex.
    J Neurosci. 2003 Nov 5;23(31):9996-10001 PMID: 14602813
  73. Specification of temporal identity in the developing nervous system.
    Annu Rev Cell Dev Biol. 2004;20:619-47 PMID: 15473854
  74. Asymmetric inheritance of radial glial fibers by cortical neurons.
    Neuron. 2001 Sep 13;31(5):727-41 PMID: 11567613
  75. A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons.
    Genes Dev. 2000 Jan 1;14(1):67-80 PMID: 10640277
  76. Human brain malformations and their lessons for neuronal migration.
    Annu Rev Neurosci. 2001;24:1041-70 PMID: 11520927
  77. Laminar patterning in the developing neocortex by temporally coordinated fibroblast growth factor signaling.
    J Neurosci. 2004 Oct 6;24(40):8711-9 PMID: 15470137
  78. A comparison of Notch, Hes and Grg expression during murine embryonic and post-natal development.
    Cell Mol Biol (Noisy-le-grand). 1999 Jul;45(5):687-708 PMID: 10512199
  79. Expression of Cux-1 and Cux-2 in the subventricular zone and upper layers II-IV of the cerebral cortex.
    J Comp Neurol. 2004 Nov 8;479(2):168-80 PMID: 15452856
  80. Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition.
    Science. 1974 Feb 1;183(4123):425-7 PMID: 4203022
  81. Separate progenitors for radial and tangential cell dispersion during development of the cerebral neocortex.
    Neuron. 1998 Aug;21(2):295-304 PMID: 9728911
  82. Increased expression of insulin-like growth factor-I (IGF-I) during embryonic development produces neocortical overgrowth with differentially greater effects on specific cytoarchitectonic areas and cortical layers.
    Brain Res Dev Brain Res. 2005 Feb 8;154(2):227-37 PMID: 15707676
  83. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors.
    Science. 2002 Jul 19;297(5580):365-9 PMID: 12130776
  84. Early ontogeny of the secondary proliferative population of the embryonic murine cerebral wall.
    J Neurosci. 1995 Sep;15(9):6058-68 PMID: 7666189
  85. Induction of deep layer cortical neurons in vitro.
    Development. 1997 Feb;124(4):915-23 PMID: 9043072
  86. Expression of the antiproliferative gene TIS21 at the onset of neurogenesis identifies single neuroepithelial cells that switch from proliferative to neuron-generating division.
    Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4639-44 PMID: 10200315
  87. Fez1 is layer-specifically expressed in the adult mouse neocortex.
    Eur J Neurosci. 2004 Dec;20(11):2909-16 PMID: 15579145
  88. Elusive radial glial cells: historical and evolutionary perspective.
    Glia. 2003 Jul;43(1):19-32 PMID: 12761862
  89. The role of notch in promoting glial and neural stem cell fates.
    Annu Rev Neurosci. 2002;25:471-90 PMID: 12052917
  90. Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation.
    Development. 2004 Nov;131(22):5539-50 PMID: 15496443
  91. Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes.
    Science. 1997 Oct 17;278(5337):474-6 PMID: 9334308
  92. Sequence of neuron origin and neocortical laminar fate: relation to cell cycle of origin in the developing murine cerebral wall.
    J Neurosci. 1999 Dec 1;19(23):10357-71 PMID: 10575033
  93. Cortical upper layer neurons derive from the subventricular zone as indicated by Svet1 gene expression.
    Development. 2001 Jun;128(11):1983-93 PMID: 11493521
  94. The Wnt/beta-catenin pathway directs neuronal differentiation of cortical neural precursor cells.
    Development. 2004 Jun;131(12):2791-801 PMID: 15142975
  95. Differential expression of Pax6 and Ngn2 between pair-generated cortical neurons.
    J Neurosci Res. 2004 Dec 15;78(6):784-95 PMID: 15523634
  96. Continuing role for mouse Numb and Numbl in maintaining progenitor cells during cortical neurogenesis.
    Nat Neurosci. 2004 Aug;7(8):803-11 PMID: 15273690
  97. Specification of cerebral cortical areas.
    Science. 1988 Jul 8;241(4862):170-6 PMID: 3291116
  98. Generating the cerebral cortical area map.
    Annu Rev Neurosci. 2003;26:355-80 PMID: 14527269
  99. Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain.
    J Comp Neurol. 2003 May 26;460(2):266-79 PMID: 12687690
  100. Each member of the Id gene family exhibits a unique expression pattern in mouse gastrulation and neurogenesis.
    Dev Dyn. 1997 Jan;208(1):92-106 PMID: 8989524
  101. Progressive restriction in fate potential by neural progenitors during cerebral cortical development.
    Development. 2000 Jul;127(13):2863-72 PMID: 10851131
  102. Heterozygous PAX6 mutation, adult brain structure and fronto-striato-thalamic function in a human family.
    Eur J Neurosci. 2004 Mar;19(6):1505-12 PMID: 15066147
  103. Beyond laminar fate: toward a molecular classification of cortical projection/pyramidal neurons.
    Dev Neurosci. 2003 Mar-Aug;25(2-4):139-51 PMID: 12966212
  104. Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2.
    Development. 2000 Oct;127(20):4361-71 PMID: 11003836
Article Info
Journal
Molecular neurobiology
Abbr.
Mol Neurobiol
ISSN
0893-7648
DOI
10.1385/MN:33:1:033
Email
rhevner@u.washington.edu
Published
2006-02-00
Pages
33-50
Language
English
Region
United States
NLM ID
8900963
Subset
IM
Grants
NINDS NIH HHS · NS045018 · United States
External Links
PubMed source DOI: 10.1385/MN:33:1:033 View journal details
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