EC Clinical and Medical Case Reports

The nervous system is derived from the ectodermal germ layer which is one of the three main germ layers of the embryo. A series of fascinating highly regulated, still highly complex molecular, cellular, and morphological changes beginning in the early embryonic period occur within the neuroepithelium. The neuroepithelium of the neural plate which is simple columnar epithelium at the beginning but pseudostratified columnar epithelium during cellular differentiation gives rise to the neurons and glial cells except for the microglia cells. Neural stem/progenitor cells expand as neuroepithelial cells by symmetric proliferative divisions and then at the onset of neurogenesis transform into radial glial cells after switching to asymmetric neurogenic divisions. The radial glial cells generate directly or indirectly all neurons and glial cells. In this mini-review, I tried to summarize the transformation of the neuroectoderm into a neural tube, the main stem/progenitor cells of the neuroepithelium, symmetrical and asymmetrical division, differentiation, and migration patterns of the neuroepithelial cells.

 Keywords: Neuroepithelium; Neurogenesis; Gliogenesis; Radial Glial Cells

1. Esrefoglu M. “Embriyoloji (Turkish)”. Ema Tip Kitabevi, Istanbul: 128-132.
2. Paridaen JTML and Huttner WB. “Neurogenesis during development of the vertebrate central nervous system”. EMBO Reports 15 (2014): 351-364.
3. Latasa MJ., et al. “Cell cycle control of Notch signaling and the functional regionalization of the neuroepithelium during vertebrate neurogenesis”. The International Journal of Developmental Biology 53 (2009): 895-908.
4. Yamaguchi Y., et al. “Live imaging of apoptosis in a novel transgenic mouse highlights its role in neural tube closure”. Journal of Cell Biology 195 (2011): 1047-1060.
5. Massa V., et al. “Do cells become homeless during neural tube closure?” Cell Cycle 8 (2009): 2479-2480.
6. Gilmore AP. “Anokisis”. Cell Death and Differentiation 12 (2005): 1473-1477.
7. Lery LA and Sive H. “Totally tubular: The mystery behind function and origin of the brain ventricular system”. Bioessays 31 (2009): 446-458.
8. Bansod S., et al. “Hes5 regulates the transition timing of neurogenesis and gliogenesis in mammalian neocortical development”. Development 144 (2017): 3156-3167.
9. Eze UC., et al. “Single-cell atlas of early human brain development highlights heterogeneity of human neuroepithelial cells and early radial glia”. Nature Neuroscience 24 (2021): 584-594.
10. Hatakeyama J., et al. “Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation”. Development 131 (2004): 5539-5550.
11. Sahara S and O’Leary DDM. “Fgf10 regulates transition period of cortical stem cell differentiation to radial glia controlling generation of neurons and basal progenitors”. Neuron 63 (2009): 48-62.
12. Lui H., et al. “Development and evolution of the human neocortex”. Cell 146 (2011): 18-36.
13. Noctor SC., et al. “Neurons derived from radial glial cells establish radial units in neocortex”. Nature 409 (2001): 714-720.
14. Noctor SC., et al. “Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases”. Nature Neuroscience 7 (2004): 136-144.
15. Noctor SC., et al. “Distinct behaviors of neural stem and progenitor cells underlie cortical neurogenesis”. The Journal of Comparative Neurology 508 (2008): 28-44.
16. Costa MR., et al. “Par-complex proteins promote proliferative progenitor divisions in the developing mouse cerebral cortex”. Development 135 (2008): 11-22.
17. Lehtinen MK and Walsh CA. “Neurogenesis at the brain-cerebrospinal fluid interface”. The Annual Review of Cell and Developmental Biology 27 (2011): 653-679.
18. Willaredt MA., et al. “Primary cilia and forebrain development”. Mechanisms of Development 130 (2013): 373-380.
19. Wilsch-Bauninger M., et al. “Basolateral rather than apical primary cilia on neuroepithelial cells committed to delamination”. Development 139 (2012): 95-105.
20. Higginbotham H., et al. “Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation”. Nature Neuroscience 16 (2013): 1000-1007.
21. Fietz SA., et al. “OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling”. Nature Neuroscience 13 (2019): 690-699.
22. Radakovits R., et al. “Regulation of radial glial survival by signals from the meninges”. The Journal of Neuroscience 29 (2009): 7694-7705.
23. Rakic P. “A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution”. Trends in Neurosciences 18 (1995): 383-388.
24. Rakic P. “Evolution of the neocortex: a perspective from developmental biology”. Nature Reviews Neuroscience 10 (2009): 724-735.
25. Yamaguchi M., et al. “Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain”. The Journal of Physiological Sciences 66 (2016): 197-2006.
26. Kosodo Y., et al. “Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells”. The EMBO Journal 23 (2004): 2314-2324.
27. Postiglione MP., et al. “Mouse inscuteable induces apical-basal spindle orientation to facilitate intermediate progenitor generation in the developing neocortex”. Neuron 72 (2011): 269-284.
28. LaMonica BE., et al. “Mitotic spindle orientation predicts outer radial glial cell generation in human neocortex”. Nature Communications 4 (2013): 1665.
29. Shitamukai A., et al. “Oblique radial glial divisions in the developing mouse neocortex induce self-renewing progenitors outside the germinal zone that resemble primate outer subventricular zone progenitors”. The Journal of Neuroscience 31 (2011): 3683-3695.
30. Malatesta P., et al. “Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage”. Development 127 (2000): 5253-5263.
31. Sun YE., et al. “Making and repairing the mammalian brain-signaling toward neurogenesis and gliogenesis”. Seminars in Cell and Developmental Biology 14 (2003): 161-168.
32. Qian X., et al. “Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells”. Neuron 28 (2000): 69-80.
33. Englund C., et al. “Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex”. The Journal of Neuroscience 25 (2005): 247-251.
34. Kowalczyk T., et al. “Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex”. Cerebral Cortex 19 (2009): 2439-2450.
35. Tarabykin V., et al. “Cortical upper layer neurons derive from the subventricular zone as indicated by Svet1 gene expression”. Development 128 (2001): 1983-1993.
36. Zimmer C., et al. “Dynamics of Cux2 expression suggests that an early pool of SVZ precursors is fated to become upper cortical layer neurons”. Cerebral Cortex 14 (2004): 1408-1420.
37. Miyata T., et al. “Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells”. Development 131 (2004): 3133-3145.
38. Fish JL., et al. “Making bigger brains-the evolution of neural-progenitor-cell division”. Journal of Cell Science 121 (2008): 2783-2793.
39. Kriegstein A., et al. “Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion”. Nature Reviews Neuroscience 7 (2006): 883-890.
40. Hansen DV., et al. “Neurogenic radial glia in the outer subventricular zone of the human neocortex”. Nature 464 (2010): 554-561.
41. Sessa A., et al. “Tbr2 directs conversion of radial glia into basal precursors and guides neuronal amplification by indirect neurogenesis in the developing neocortex”. Neuron 60 (2008): 56-69.
42. Stancik EK., et al. “Heterogeneity in ventricular zone neural precursors contributes to neuronal fate diversity in the postnatal neocortex”. The Journal of Neuroscience 30 (2010): 7028-7036.
43. MuhChyi C., et al. “Epigenetic regulation of neural stem cell fate during corticogenesis”. International Journal of Developmental Neuroscience 31 (2013): 424-433.
44. Desai AR and McConnell SK. “Progressive restriction in fate potential by neural progenitors during cerebral cortical development”. Development 127 (2000): 2863-2872.
45. Frantz GD and McConnell SK. “Restriction of late cerebral cortical progenitors to an upper-layer fate”. Neuron 17 (1996): 55-61.
46. Rakic P. “Specification of cerebral cortical areas”. Science 241 (1988): 170-176.
47. Rakic P. “Radial unit hypothesis of neocortical expansion”. Novartis Foundation Symposia 228 (2000): 30-42.
48. Rakic P. “Mode of cell migration to the superficial layers of fetal monkey neocortex”. The Journal of Comparative Neurology 145 (1972): 61-83.
49. Choi BH. “Glial fibrillary acidic protein in radial glia of early human fetal cerebrum: a light and electron microscopic immunoperoxidase study”. Journal of Neuropathology and Experimental Neurology 45 (1986): 408-418.
50. Alvarez-Buylla A., et al. “Identification of neural stem cells in the adult vertebrate brain”. Brain Research Bulletin 57 (2002): 751-758.
51. Doetsch F. “The glial identity of neural stem cells”. Nature Neuroscience 6 (2003): 1127-1134.
52. Raponi E., et al. “S100B expression defines a state in which GFAP-expressing cells lose their neural stem cell potential and acquire a more mature developmental stage”. Glia 55 (2007): 165-177.
53. Nikolopoulou E., et al. “Neural tube closure: cellular, molecular and biomechanical mechanisms”. Development 144 (2017): 552-566.
54. Taverna E and Huttner WB. “Neural progenitor nuclei IN motion”. Neuron 67 (2010): 906-914.
55. Murciano A., et al. “Interkinetic nuclear movement may provide spatial clues to the regulation of neurogenesis”. Molecular and Cellular Neuroscience 21 (2002): 285-300.
56. Webster W and Langman J. “The effect of cytochalasin B on the neuroepithelial cells of the mouse embryo”. The American Journal of Anatomy 152 (1978): 209-221.
57. Xie Z., et al. “Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool”. Neuron 56 (2007): 79-93.
58. Rowitch DH and Kriegstein AR. “Developmental genetics of vertebrate glial-cell specification”. Nature 468 (2010): 214-222.
59. Zuchero JB and Barres BA. “Glia in mammalian development and disease”. Develeopment 142 (2015): 3805-3809.
60. Bergles DE and Richardson WD. “Oligodendrocyte development”. Cold Spring Harbor Perspectives in Biology 8 (2016): a020453.
61. Lu PPY and Ramanan N. “A critical cell-intrinsic role for serum response factor in glial specification in the CNS”. The Journal of Neuroscience 32 (2012): 8012-8023.
62. Morrow T., et al. “Sequential specification of neurons and glia by developmentally regulated extracellular factors”. Development 128 (2001): 3585-3594.
63. Ohtsuka T and Kageyama R. “Regulation of temporal properties of neural stem cells and transition timing of neurogenesis and gliogenesis during mammalian neocortical development”. Seminars in Cell and Developmental Biology 95 (2019): 4-11.
64. Bhardwaj RD., et al. “Neocortical neurogenesis in humans is restricted to development”. Proceedings of the National Academy of Sciences of the United States of America 103 (2006): 12564-12568.
65. Yeung MS., et al. “Dynamics of oligodendrocyte generation and myelination in the human brain”. Cell 159 (2014): 766-774.
66. Stolt CC., et al. “The sox9 transcription factor determines glial fate choice in the developing spinal cord”. Genes and Development 17 (2003): 1677-1689.
67. Molofsky AV., et al. “Mechanisms of astrocyte development; Patterning and Cell Type Specification in the Developing Cns and Pns”. International Journal of Developmental Neuroscience (2013): 723-742.
68. Sauvageot CM and Stiles CD. “Molecular mechanisms controlling cortical gliogenesis”. Current Opinion in Neurobiology 12 (2002): 244-249.
69. Doetsch F., et al. “Subventricular zone astrocytes are neural stem cells in the adult mammalian brain”. Cell 97 (1999): 703-716.
70. Kondo T and Raff M. “Oligodendrocyte precursor cells reprogrammed to become multipotential NS stem cells”. Science 289 (2000): 1754-1757.
71. Nieto M., et al. “Neural bHLH genes control the neuronal versus glial fate decision in cortical progenitors”. Neuron 29 (2001): 401-413.
72. Molofsky AV and Deneen B. “Astrocyte Development: A Guide for the Perplexed”. Glia 63 (2015): 1320-1329.
73. Heins N., et al. “Glial cells generate neurons: The role of the transcription factor pax6”. Nature Neuroscience 5 (2002): 308-315.
74. Berninger B., et al. “Functional properties of neurons derived from in vitro reprogrammed postnatal astroglia”. The Journal of Neuroscience 27 (2007): 8654-8664.
75. Torper O., et al. “Generation of induced neurons via direct conversion in vivo”. Proceedings of the National Academy of Sciences of the United States of America 110 (2013): 7038-7043.
76. Magavi S., et al. “Coincident generation of pyramidal neurons and protoplasmic astrocytes in neocortical columns”. The Journal of Neuroscience 32 (2012): 4762-4772.
77. Levison SW., et al. “The migrational patterns and developmental fates of glial precursors in the rat subventricular zone are temporally regulated”. Development 119 (1993): 611-622.
78. Akdemir ES., et al. “Astrocytogenesis: where, when, and how”. F1000Research 9 (2020).
79. Masahira N., et al. “Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells”. Developmental Biology 293 (2006): 358-369.
80. Bayraktar OA., et al. “Astrocyte development and heterogeneity”. Cold Spring Harbor Perspectives in Biology 7 (2014): a020362.
81. Middeldorp J and Hol EM. “GFAP in health and disease”. Progress in Neurobiology 93 (2011): 421-443.
82. Foo LC and Dougherty JD. “Aldh1L1 is expressed by postnatal neural stem cells in vivo”. Glia 61 (2013): 1533-1541.
83. Scholze AR., et al. “BMP signaling in astrocytes downregulates EGFR to modulate survival and maturation”. PLoS ONE 9 (2014): e110668.
84. Pringle NP and Richardson WD. “A singularity of PDGF are ceptor expression in the dorsoventral axis of the neural tube may define the origin of the oligodendrocyte lineage”. Development 117 (1993): 525-533.
85. Hajihosseini M., et al. “Origin of oligodendrocytes within the human spinal cord”. The Journal of Neuroscience 16 (1996): 7981-7994.
86. Park HC and Appel B. “Delta-Notch signaling regulates oligodendrocyte specification”. Development 130 (2003): 3747-3755.
87. Kim H., et al. “Notch-regulated oligodendrocyte specification from radial glia in the spinal cord of zebrafish embryos”. Developmental Dynamics 237 (2008): 2081-2089.
88. Wang S., et al. “Notch receptor activation inhibits oligodendrocyte differentiation”. Neuron 21 (1998): 63-75.