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Population Dynamics During Cell Proliferation and Neuronogenesis in the Developing Murine Neocortex

  • Richard S. Nowakowski
  • Verne S. CavinessJr
  • Takao Takahashi
  • Nancy L. Hayes
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 39)

Summary

During the development of the neocortex, cell proliferation occurs in two specialized zones adjacent to the lateral ventricle. One of these zones, the ventricular zone, produces most of the neurons of the neocortex. The proliferating population that resides in the ventricular zone is a pseudostratified ventricular epithelium (PVE) that looks uniform in routine histological preparations, but is, in fact, an active and dynamically changing population. In the mouse, over the course of a 6-day period, the PVE produces approximately 95% of the neurons of the adult neocortex. During this time, the cell cycle of the PVE population lengthens from about 8 h to over 18 h and the progenitor population passes through a total of 11 cell cycles. This 6-day, 11-cell cycle period comprises the “neuronogenetic interval” (NI). At each passage through the cell cycle, the proportion of daughter cells that exit the cell cycle (Q cells) increases from 0 at the onset of the NI to 1 at the end of the NI. The proportion of daughter cells that re-enter the cell cycle (P cells) changes in a complementary fashion from 1 at the onset of the NI to 0 at the end of the NI. This set of systematic changes in the cell cycle and the output from the proliferative population of the PVE allows a quantitative and mathematical treatment of the expansion of the PVE and the growth of the cortical plate that nicely accounts for the observed expansion and growth of the developing neocortex. In addition, we show that the cells produced during a 2-h window of development during specific cell cycles reside in a specific set of laminae in the adult cortex, but that the distributions of the output from consecutive cell cycles overlap. These dynamic events occur in all areas of the PVE underlying the neocortex, but there is a gradient of maturation that begins in the rostrolateral neocortex near the striatotelencephalic junction and which spreads across the surface of the neocortex over a period of 24–36 h. The presence of the gradient across the hemisphere is a possible source of positional information that could be exploited during development to establish the areal borders that characterize the adult neocortex.

Keywords

Ventricular Zone Cortical Plate Cereb Cortex Proliferative Population Stern Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Angevine JBJ, Sidman RL (1961) Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse. Nature 192:766–768PubMedCrossRefGoogle Scholar
  2. Beaulieu C (1993) Numerical data on neocortical neurons in adult rat, with special reference to the GABA population. Brain Res 609:284–292PubMedCrossRefGoogle Scholar
  3. Beaulieu C, Colonnier M (1989) Number of neurons in individual laminae of areas 3B, 4 gamma, and 6a alpha of the cat cerebral cortex: a comparison with major visual areas. J Comp Neurol 279:228–234PubMedCrossRefGoogle Scholar
  4. Bittman KS, LoTurco JJ (1999) Differential regulation of connexin 26 and 43 in murine neocortical precursors. Cereb Cortex 9:188–195PubMedCrossRefGoogle Scholar
  5. Bittman KS, Owens DF, Kriegstein AR, LoTurco JJ (1997) Cell coupling and uncoupling in the ventricular zone of developing neocortex. J Neurosci 17:7037–7044PubMedGoogle Scholar
  6. Blau HM, Brazelton TR, Weimann JM (2001) The evolving concept of a stem cell: entity or function? Cell 105:829–841PubMedCrossRefGoogle Scholar
  7. Boulder Committee (1970) Embryonic vertebrate central nervous system: revised terminology. Anat Rec 166:257–262CrossRefGoogle Scholar
  8. Brodmann K (1909) Vergleichende Lokalisationslehre der Grosshirnrinde. Barth, LeipzigGoogle Scholar
  9. Cai L, Hayes NL, Nowakowski RS (1997) Local homogeneity of cell cycle length in developing mouse cortex. J Neurosci 17:2079–2087PubMedGoogle Scholar
  10. Caviness VS, Sidman RL (1973) Time of origin of corresponding cell classes in the cerebral cortex of normal and reeler mutant mice: an autoradiographic analysis. J Comp Neurol 148:141–152PubMedCrossRefGoogle Scholar
  11. Caviness VS, Takahashi T, Nowakowski R (1995) Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model. Trends Neurosci 18:379–383PubMedCrossRefGoogle Scholar
  12. Caviness VS Jr, Takahashi T, Nowakowski RS (2000) Neuronogenesis and the early events of neocortical histogenesis. Res Prob Cell Differ 30:107–143Google Scholar
  13. Caviness VSJ (1975) Architectonic map of neocortex of the normal mouse. J Comp Neurol 164: 247–264PubMedCrossRefGoogle Scholar
  14. Chenn A, McConnell S (1995) Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis. Cell 82:631–641PubMedCrossRefGoogle Scholar
  15. Chenn A, Zhang YA, Chang BT, McConnell SK (1998) Intrinsic polarity of mammalian neuroepithelial cells. Mol Cell Neurosci 11:183–193PubMedCrossRefGoogle Scholar
  16. Cunningham JJ, Roussel MF (2001) Cyclin-dependent kinase inhibitors in the development of the central nervous system. Cell Growth Differ 12:387–396PubMedGoogle Scholar
  17. De Carlos JA, O’Leary DD (1992) Growth and targeting of subplate axons and establishment of major cortical pathways. J Neurosci 12:1194–1211PubMedGoogle Scholar
  18. Delalle I, Takahashi T, Nowakowski RS, Tsai LH, Caviness VS Jr (1999) Cyclin E-p27 opposition and regulation of the G1 phase of the cell cycle in the murine neocortical PVE: a quantitative analysis of mRNA in situ hybridization. Cereb Cortex 9:824–832PubMedCrossRefGoogle Scholar
  19. Drago J, Murphy M, Carroll SM, Harvey RP, Bartlett PF (1991) Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I. Proc Natl Acad Sci USA 88:2199–2203PubMedCrossRefGoogle Scholar
  20. Erzurumlu RS, Jhaveri S (1992) Emergence of connectivity in the embryonic rat parietal cortex. Cereb Cortex 2:336–352PubMedCrossRefGoogle Scholar
  21. Ghosh A, Greenberg ME (1995) Distinct roles for bFGF and NT-3 in the regulation of cortical neurogenesis. Neuron 15:89–103PubMedCrossRefGoogle Scholar
  22. Gratzner HG (1982) Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: a new reagent for detection of DNA replication. Science 218:474–478PubMedCrossRefGoogle Scholar
  23. Hamilton E, Dobbin J (1983a) The percentage labeled mitosis technique shows the mean cell cycle time to be half its true value in carcinoma TY. I. [H3]Thymidine and vincristine studies. Cell Tissue Kinet 16:473–482PubMedGoogle Scholar
  24. Hamilton E, Dobbin J (1983b) The percentage labeled mitosis technique shows the mean cell cycle time to be half its true value in carcinoma NT. II. [3H]Deoxyuridine studies. Cell Tissue Kinet 16:483–492PubMedGoogle Scholar
  25. Haug H (1987) Brain sizes, surfaces, and neuronal sizes of the cortex cerebri: a stereological investigation of man and his variability and a comparison with some mammals (primates, whales, marsupials, insectivores, and one elephant). Am J Anat 180:126–142PubMedCrossRefGoogle Scholar
  26. Hayes NL, Nowakowski RS (2000) Exploiting the dynamics of S-phase tracers in developing brain: interkinetic nuclear migration for cells entering versus leaving the S-phase. Dev Neurosci 22: 44–55PubMedCrossRefGoogle Scholar
  27. Hoshino K, Matsuzawa T, Murakami U (1973) Characteristic of the cell cycle of matrix cells in the mouse embryo during histogenesis of telencephalon. Exp Cell Res 77:89–94PubMedCrossRefGoogle Scholar
  28. Kaufmann SL (1968) Lengthening of the generation cycle during embryonic differentiation of the mouse neural tube. Exp Cell Res 49:420–424CrossRefGoogle Scholar
  29. Miller MW, Nowakowski RS (1988) Use of bromodeoxyuridine-immunohistochemistry to examine the proliferation, migration and time of origin of cells in the central nervous system. Brain Res 457:44–52PubMedCrossRefGoogle Scholar
  30. Mitsuhashi T, Aoki Y, Eksioglu YZ, Takahashi T, Bhide PG, Reeves SA, Caviness VS Jr (2001) Over-expression of p27Kip1 lengthens the G1 phase in a mouse model that targets inducible gene expression to central nervous system progenitor cells. Proc Natl Acad Sci USA 98:6435–6440PubMedCrossRefGoogle Scholar
  31. Miyama S, Takahashi T, Nowakowski RS, Caviness VS Jr (1997) A gradient in the duration of the G1 phase in the murine neocortical proliferative epithelium. Cereb Cortex 7:678–689PubMedCrossRefGoogle Scholar
  32. Molnar Z, Blakemore C (1995) How do thalamic axons find their way to the cortex? Trends Neurosci 18:389–397PubMedCrossRefGoogle Scholar
  33. Nicot A, DiCicco-Bloom E (2001) Regulation of neuroblast mitosis is determined by PACAP receptor isoform expression. Proc Natl Acad Sci USA 98:4758–4763PubMedCrossRefGoogle Scholar
  34. Nowakowski RS, Rakic P (1974) Clearance rate of exogenous 3H-thymidine from the plasma of pregnant rhesus monkeys. Cell Tissue Kinet 7:189–194PubMedGoogle Scholar
  35. Nowakowski RS, Rakic P (1975) Time of origin of neurons in the hippocampal region of the rhesus monkey. Neurosci Abstr 1:773Google Scholar
  36. Nowakowski RS, Lewin SB, Miller MW (1989) Bromodeoxyuridine immunohistochemical determination of the lengths of the cell cycle and the DNA-synthetic phase for an anatomically defined population. J Neurocytol 18:311–318PubMedCrossRefGoogle Scholar
  37. Owens DF, Liu X, Kriegstein AR (1999) Changing properties of GABA(A) receptor-mediated signaling during early neocortical development. J Neurophysiol 82:570–583PubMedGoogle Scholar
  38. Owens DF, Flint AC, Dammerman RS, Kriegstein AR (2000) Calcium dynamics of neocortical ventricular zone cells. Dev Neurosci 22:25–33PubMedCrossRefGoogle Scholar
  39. Raballo R, Rhee J, Lyn-Cook R, Leckman JF, Schwartz ML, Vaccarino FM (2000) Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. J Neurosci 20:5012–5023PubMedGoogle Scholar
  40. Rakic P (1974) Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition. Science 183:425–427PubMedCrossRefGoogle Scholar
  41. Rockel AJ, Hiorns RW, Powell TP (1974) Proceedings: numbers of neurons through full depth of neocortex. J Anat 118:371PubMedGoogle Scholar
  42. Rockel AJ, Hiorns RW, Powell TP (1980) The basic uniformity in structure of the neocortex. Brain 103:221–244PubMedCrossRefGoogle Scholar
  43. Rothe M, Pehl M, Taubert H, Jackie H (1992) Loss of gene function through rapid mitotic cycles in the Drosophila embryo. Nature 359:156–159PubMedCrossRefGoogle Scholar
  44. Sauer FC (1936) The interkinetic migration of embryonic epithelial nuclei. J Morphol 60:1–11CrossRefGoogle Scholar
  45. Sidman RL (1970) Autoradiographic methods and principles for study of the nervous system with thymidine-H3. In: Nauta WJH, Ebbesson SOE (eds) Contemporary research methods in neuroanatomy. Springer, Berlin Heidelberg New York, pp 252–274CrossRefGoogle Scholar
  46. Sidman RL, Miale IL, Feder N (1959) Cell proliferation and migration in the primitive ependymal zone: an autoradiographic study of histogenesis in the nervous system. Exp Neurol 1:322–333PubMedCrossRefGoogle Scholar
  47. Stanfield BB, Cowan WM (1979) The development of the hippocampus and dentate gyrus in normal and reeler mice. J Comp Neurol 185:423–459PubMedCrossRefGoogle Scholar
  48. Suh J, Lu N, Nicot A, Tatsuno I, DiCicco-Bloom E (2001) PACAP is an anti-mitogenic signal in developing cerebral cortex. Nat Neurosci 4:123–124PubMedCrossRefGoogle Scholar
  49. Takahashi T, Nowakowski RS, Caviness VS Jr (1992) BUdR as an S-phase marker for quantitative studies of cytokinetic behaviour in the murine cerebral ventricular zone. J Neurocytol 21:185–197PubMedCrossRefGoogle Scholar
  50. Takahashi T, Nowakowski RS, Caviness VS Jr (1993) Cell cycle parameters and patterns of nuclear movement in the neocortical proliferative zone of the fetal mouse. J Neurosci 13:820–833PubMedGoogle Scholar
  51. Takahashi T, Nowakowski RS, Caviness VS Jr (1995) The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall. J Neurosci 15:6046–6057PubMedGoogle Scholar
  52. Takahashi T, Nowakowski RS, Caviness VS Jr (1996) The leaving or Q fraction of the murine cerebral proliferative epithelium: a general model of neocortical neuronogenesis. J Neurosci 16:6183–6196PubMedGoogle Scholar
  53. Takahashi T, Nowakowski RS, Caviness VS Jr (2001) Neocortical neuronogenesis: regulation, control points and a strategy of structural variation. In: Nelson CA, Luciana M (eds) Handbook of cognitive developmental neuroscience. MIT Press, Cambridge, MA, pp 3–22Google Scholar
  54. Tennyson CN, Klamut HJ, Worton RG (1995) The human dystrophin gene requires 16 hours to be transcribed and is cotranscriptionally spliced. Nat Genet 9:184–190PubMedCrossRefGoogle Scholar
  55. Vaccarino FM, Schwartz ML, Raballo R, Rhee J, Lyn-Cook R (1999a) Fibroblast growth factor signaling regulates growth and morphogenesis at multiple steps during brain development. Curr Top Dev Biol 46:179–200PubMedCrossRefGoogle Scholar
  56. Vaccarino FM, Schwartz ML, Raballo R, Nilsen J, Rhee J, Zhou M, Doetschman T, Coffin JD, Wyland J J, Hung YT (1999b) Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nat Neurosci 2:848PubMedCrossRefGoogle Scholar
  57. Zindy F, Cunningham JJ, Sherr CJ, Jogal S, Smeyne RJ, Roussel MF (1999) Postnatal neuronal proliferation in mice lacking Ink4d and Kip1 inhibitors of cyclin-dependent kinases. Proc Natl Acad Sci USA 96:13462–13467PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • Richard S. Nowakowski
    • 1
  • Verne S. CavinessJr
    • 2
  • Takao Takahashi
    • 3
  • Nancy L. Hayes
    • 1
  1. 1.Department of Neuroscience and Cell BiologyUMDNJ-Robert Wood Johnson Medical SchoolPiscatawayUSA
  2. 2.Pediatric Neurology ServiceMassachusetts General HospitalBostonUSA
  3. 3.Department of PediatricsKeio University School of MedicineShinjuku-ku, Tokyo 160Japan

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