The Leaving or Q Fraction of the Murine Cerebral Proliferative Epithelium: A General Model of Neocortical Neuronogenesis

Neurons of neocortical layers II–VI in the dorsomedial cortex of the mouse arise in the pseudostratified ventricular epithelium (PVE) through 11 cell cycles over the six embryonic days 11–17 (E11–E17). The present experiments measure the proportion of daughter cells that leave the cycle (quiescent or Q fraction or Q) during a single cell cycle and the complementary proportion that continues to proliferate (proliferative or P fraction or P; P = 1 − Q). Q and P for the PVE become 0.5 in the course of the eighth cycle, occurring on E14, and Q rises to ∼0.8 (and P falls to ∼0.2) in the course of the 10th cycle occurring on E16. This indicates that early in neuronogenesis, neurons are produced relatively slowly and the PVE expands rapidly but that the reverse happens in the final phase of neuronogenesis. The present analysis completes a cycle of analyses that have determined the four fundamental parameters of cell proliferation: growth fraction, lengths of cell cycle, and phases Q and P. These parameters are the basis of a coherent neuronogenetic model that characterizes patterns of growth of the PVE and mathematically relates the size of the initial proliferative population to the neuronal population of the adult neocortex.

[1]  T Takahashi,et al.  BUdR as an S-phase marker for quantitative studies of cytokinetic behaviour in the murine cerebral ventricular zone , 1992, Journal of neurocytology.

[2]  J G Parnavelas,et al.  Separate progenitor cells give rise to pyramidal and nonpyramidal neurons in the rat telencephalon. , 1991, Cerebral cortex.

[3]  S. Mcconnell,et al.  Cleavage orientation and the asymmetric inheritance of notchl immunoreactivity in mammalian neurogenesis , 1995, Cell.

[4]  A. Blaschke,et al.  Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex. , 1996, Development.

[5]  D. Price,et al.  Evidence that the earliest generated cells of the murine cerebral cortex form a transient population in the subplate and marginal zone. , 1992, Brain research. Developmental brain research.

[6]  P. Gressens,et al.  Early Neurogenesis and Teratogenesis in Whole Mouse Embryo Cultures. Histochemical, Immunocytological and Ultrastructural Study of the Premigratory Neuronal‐glial Units in Normal Mouse Embryo and in Mouse Embryos Influenced by Cocaine and Retinoic Acid , 1992, Journal of neuropathology and experimental neurology.

[7]  F. C. Sauer.  Mitosis in the neural tube , 1935 .

[8]  B. Finlay,et al.  Linked regularities in the development and evolution of mammalian brains. , 1995, Science.

[9]  P. Rakic.  Specification of cerebral cortical areas. , 1988, Science.

[10]  T. Powell,et al.  The basic uniformity in structure of the neocortex. , 1980, Brain : a journal of neurology.

[11]  V. Caviness,et al.  Mode of cell proliferation in the developing mouse neocortex. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[12]  V. Caviness,et al.  Early ontogeny of the secondary proliferative population of the embryonic murine cerebral wall , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  C. Cepko,et al.  Cellular migration patterns in the developing mouse cerebral cortex. , 1990, Development.

[14]  C. Cepko,et al.  Clonally related cortical cells show several migration patterns. , 1988, Science.

[15]  W. His.  Die Neuroblasten und deren Entstehung im embryonalen Mark , 1889 .

[16]  B. Finlay,et al.  Control of cell number in the developing mammalian visual system , 1989, Progress in Neurobiology.

[17]  V. Caviness,et al.  The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  S. Fujita.  The matrix cell and cytogenesis in the developing central nervous system , 1963, The Journal of comparative neurology.

[19]  P. Rakić.  Neurons in Rhesus Monkey Visual Cortex: Systematic Relation between Time of Origin and Eventual Disposition , 1974, Science.

[20]  R. von Waechter,et al.  Generation times of the matrix cells during embryonic brain development: an autoradiographic study in rats. , 1972, Brain research.

[21]  B L Finlay,et al.  Local differences in the amount of early cell death in neocortex predict adult local specializations. , 1983, Science.

[22]  J. Parnavelas,et al.  Lineage analysis reveals neurotransmitter (GABA or glutamate) but not calcium-binding protein homogeneity in clonally related cortical neurons , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  V. Caviness,et al.  Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model , 1995, Trends in Neurosciences.

[24]  C. Cepko,et al.  Clonal dispersion in proliferative layers of developing cerebral cortex , 1993, Nature.

[25]  J. Price.  Cell lineage in the rat cerebral cortex , 1992, Neurochemistry International.

[26]  V. Caviness,et al.  Cell cycle parameters and patterns of nuclear movement in the neocortical proliferative zone of the fetal mouse , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[27]  P. Rakić,et al.  Neuronal migration, with special reference to developing human brain: a review. , 1973, Brain research.

[28]  J. Sanes,et al.  Cell lineage in the cerebral cortex of the mouse studied in vivo and in vitro with a Recombinant Retrovirus , 1988, Neuron.

[29]  C. Walsh,et al.  Systematic widespread clonal organization in cerebral cortex , 1995, Neuron.

[30]  C. Shatz,et al.  Neurogenesis of the cat's primary visual cortex , 1985, The Journal of comparative neurology.

[31]  P. Rakić,et al.  The site of origin and route and rate of migration of neurons to the hippocampal region of the rhesus monkey , 1981, The Journal of comparative neurology.

[32]  D. van der Kooy,et al.  Variability and partial synchrony of the cell cycle in the germinal zone of the early embryonic cerebral cortex , 1995, The Journal of comparative neurology.

[33]  M E SAUER,et al.  Radioautographic Study of Interkinetic Nuclear Migration in the Neural Tube.∗ , 1959, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[34]  C. Cepko.  Retrovirus vectors and their applications in neurobiology , 1988, Neuron.

[35]  C. Cepko,et al.  Widespread dispersion of neuronal clones across functional regions of the cerebral cortex. , 1992, Science.

[36]  V. Caviness.  Neocortical histogenesis in normal and reeler mice: a developmental study based upon [3H]thymidine autoradiography. , 1982, Brain research.

[37]  G. Palm,et al.  Density of neurons and synapses in the cerebral cortex of the mouse , 1989, The Journal of comparative neurology.