Pre- and post-mitotic events contribute to the progressive acquisition of area-specific connectional fate in the neocortex.

The adult primary motor cortex (area 6) is characterized by a stronger projection to the spinal cord than the primary somatosensory cortex (area 3). Here we have explored the progressive and regressive phenomena that determine these areal differences in the number of corticospinal neurons (CSNs). CSNs were birthdated with [(3)H]thymidine and subsequently retrogradely labeled from the spinal cord. The time window of CSN production is identical in both areas. The probability that a cohort of neuroblasts project to the spinal cord is indicated by the percentage of [(3)H]thymidine-positive neurons that can be back-labeled from the spinal cord. In the neonate this fate index is significantly higher in area 6 compared with area 3, indicating that early regionalization of cell fate contributes to areal differences in CSN number. In neonatal reeler mice, an increase in CSN number was accompanied by an increased fate index, showing that the integrity of the post-mitotic environment is required for the specification of the appropriate number of neurons expressing a given connectional phenotype. Postnatal development in reeler and normal is characterized by an area-specific elimination of CSN axons, which reduces areal differences in CSN number. These results show a progressive acquisition of CSN fate in the neocortex and indicate that both early regionalization and late environmental signals contribute to determining areal differences of connectional phenotype.

[1]  H. Kennedy,et al.  The timetable of laminar neurogenesis contributes to the specification of cortical areas in mouse isocortex , 1997, The Journal of comparative neurology.

[2]  Y. Arimatsu,et al.  Cogeneration of neurons with a unique molecular phenotype in layers V and VI of widespread lateral neocortical areas in the rat , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  S. Tole,et al.  Regionalization of the developing forebrain: a comparison of FORSE-1, Dlx-2, and BF-1 , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  W. Cowan,et al.  Evidence that the early postnatal restriction of the cells of origin of the callosal projection is due to the elimination of axonal collaterals rather than to the death of neurons. , 1981, Brain research.

[5]  J. Parnavelas,et al.  Neurons, astrocytes, and oligodendrocytes of the rat cerebral cortex originate from separate progenitor cells: an ultrastructural analysis of clonally related cells , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  P. C. Murphy,et al.  Cerebral Cortex , 2017, Cerebral Cortex.

[7]  C. Shatz,et al.  Synaptic Activity and the Construction of Cortical Circuits , 1996, Science.

[8]  M. Cavanagh,et al.  Transient expression of neurotransmitters in the developing neocortex , 1988, Trends in Neurosciences.

[9]  J. Rubenstein,et al.  Early neocortical regionalization in the absence of thalamic innervation. , 1999, Science.

[10]  P. Levitt,et al.  Age-dependent specification of the corticocortical connections of cerebral grafts , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  G. Leuba,et al.  NEURONAL DEATH IN THE DEVELOPMENT AND AGING OF THE CEREBRAL CORTEX OF THE MOUSE , 1981, Neuropathology and applied neurobiology.

[12]  S. Mcconnell,et al.  Restriction of Late Cerebral Cortical Progenitors to an Upper-Layer Fate , 1996, Neuron.

[13]  M. Shimada,et al.  Development of corticospinal tract fibers and their plasticity I: Quantitative analysis of the developing corticospinal tract in mice , 1996, Brain and Development.

[14]  M. Ishida,et al.  Corticocortical associative neurons expressing latexin: specific cortical connectivity formed in vivo and in vitro. , 1999, Cerebral cortex.

[15]  U. Murakami,et al.  Charasteristics of the cell cycle of matrix cells in the mouse embryo during histogenesis of telencephalon. , 1973, Experimental cell research.

[16]  H. Kennedy,et al.  Regulation of Neuroblast Cell-Cycle Kinetics Plays a Crucial Role in the Generation of Unique Features of Neocortical Areas , 1997, The Journal of Neuroscience.

[17]  P. Goldman-Rakic,et al.  Early phenotype expression of cortical neurons: evidence that a subclass of migrating neurons have callosal axons. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Brent B. Stanfield,et al.  Selective collateral elimination in early postnatal development restricts cortical distribution of rat pyramidal tract neurones , 1982, Nature.

[19]  D. O'Leary,et al.  Regulation of area identity in the mammalian neocortex by Emx2 and Pax6. , 2000, Science.

[20]  V. Caviness.  Architectonic map of neocortex of the normal mouse , 1975, The Journal of comparative neurology.

[21]  B. Finlay,et al.  Regressive events in brain development and scenarios for vertebrate brain evolution. , 1987, Brain, behavior and evolution.

[22]  H. Korr,et al.  Cell Kinetic Studies of Different Cell Types In the Developing and Adult Brain of the Rat and the Mouse: A Review , 1981, Cell and tissue kinetics.

[23]  C. Beaulieu,et al.  Equivalent cell density in three areas of neonatal rat cerebral cortex , 1994, Neuroscience Letters.

[24]  H. Kennedy,et al.  Cortical specification of mice and men. , 1993, Cerebral cortex.

[25]  D. O'Leary,et al.  Selective elimination of axons extended by developing cortical neurons is dependent on regional locale: experiments utilizing fetal cortical transplants , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  H. Kennedy,et al.  Transient cortical pathways in the pyramidal tract of the neonatal ferret , 1993, The Journal of comparative neurology.

[27]  M. Tarbit,et al.  Formation and loss of DNA in intestinal epithelium. , 1969, Journal of cell science.

[28]  S. Mcconnell,et al.  Tangential migration of neurons in the developing cerebral cortex. , 1995, Development.

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

[30]  D. O'Leary,et al.  Occipital cortical neurons with transient pyramidal tract axons extend and maintain collaterals to subcortical but not intracortical targets , 1985, Brain Research.

[31]  P. Rakić.  Kinetics of proliferation and latency between final cell division and onset of differentiation of cerebellar stellate and basket neurons , 1973, The Journal of comparative neurology.

[32]  P. Dederen,et al.  An anterograde tracer study of the developing corticospinal tract in the rat: three components. , 1987, Brain research.

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

[34]  B. Cragg,et al.  The development of synapses in the visual system of the cat , 1975, The Journal of comparative neurology.

[35]  T. Jessell,et al.  Progression from Extrinsic to Intrinsic Signaling in Cell Fate Specification A View from the Nervous System , 1999, Cell.

[36]  G M Innocenti,et al.  Growth and reshaping of axons in the establishment of visual callosal connections. , 1981, Science.

[37]  D. O'Leary,et al.  A transient pyramidal tract projection from the visual cortex in the hamster and its removal by selective collateral elimination. , 1986, Brain research.

[38]  P. Levitt,et al.  Mechanisms specifying area fate in cortex include cell-cycle-dependent decisions and the capacity of progenitors to express phenotype memory. , 1997, Development.

[39]  C. V. van Eden,et al.  An anterograde tracer study on the development of corticospinal projections from the medial prefrontal cortex in the rat. , 1989, Brain research. Developmental brain research.

[40]  T. Reh.  Cell-specific regulation of neuronal production in the larval frog retina , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[41]  M. Roger,et al.  Topographic distribution of efferent fibers originating from homotopic or heterotopic transplants: heterotopically transplanted neurons retain some of the developmental characteristics corresponding to their site of origin. , 1994, Brain research. Developmental brain research.

[42]  D. O'Leary,et al.  Cortical axons branch to multiple subcortical targets by interstitial axon budding: Implications for target recognition and “waiting periods” , 1988, Neuron.

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

[44]  P. Levitt,et al.  Progressive acquisition of cortical phenotypes as a mechanism for specifying the developing cerebral cortex. , 1993, Perspectives on developmental neurobiology.

[45]  F. Valverde,et al.  Persistence of early-generated neurons in the rodent subplate: assessment of cell death in neocortex during the early postnatal period , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  P. Levitt,et al.  The early commitment of fetal neurons to the limbic cortex , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[47]  S. Mcconnell,et al.  Cell cycle dependence of laminar determination in developing neocortex. , 1992, Science.

[48]  T. Jessell,et al.  Motor Neuron–Derived Retinoid Signaling Specifies the Subtype Identity of Spinal Motor Neurons , 1998, Cell.

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

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

[51]  J. Leckman,et al.  Basic fibroblast growth factor increases the number of excitatory neurons containing glutamate in the cerebral cortex. , 1995, Cerebral cortex.

[52]  V S Caviness,et al.  Patterns of cell and fiber distribution in the neocortex of the reeler mutant mouse , 1976, The Journal of comparative neurology.

[53]  D. O'Leary.  Development of connectional diversity and specificity in the mammalian brain by the pruning of collateral projections , 1992, Current Opinion in Neurobiology.

[54]  D. Price,et al.  The Fates of Cells in the Developing Cerebral Cortex of Normal and Methylazoxymethanol Acetate‐lesioned Mice , 1993, The European journal of neuroscience.

[55]  H. Kennedy,et al.  Neurogenesis and Commitment of Corticospinal Neurons inreeler , 1998, The Journal of Neuroscience.

[56]  Michel Cohen-Tannoudji,et al.  Early determination of a mouse somatosensory cortex marker , 1994, Nature.

[57]  T. Terashima,et al.  The intracortical position of pyramidal tract neurons in the motor cortex of the reeler changes from postnatal day 10 to adulthood. , 1991, Brain research. Developmental brain research.

[58]  H. Killackey,et al.  Subcortical projections from ectopic neocortical neurons. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[59]  X. M. Xu,et al.  Postnatal growth of corticospinal axons in the spinal cord of developing mice. , 1999, Brain research. Developmental brain research.

[60]  G. Innocenti.  Exuberant development of connections, and its possible permissive role in cortical evolution , 1995, Trends in Neurosciences.

[61]  M. Wassef,et al.  Specification of Somatosensory Area Identity in Cortical Explants , 1999, The Journal of Neuroscience.

[62]  Bonaventura Cavalieri,et al.  Geometria degli indivisibili , 1966 .

[63]  Dr. Kyrill Yurjevich Reznikov.  Cell Proliferation and Cytogenesis in the Mouse Hippocampus , 2012, Advances in Anatomy Embryology and Cell Biology.

[64]  C. Gilbert.  Microcircuitry of the visual cortex. , 1983, Annual review of neuroscience.

[65]  M. Abercrombie.  Estimation of nuclear population from microtome sections , 1946, The Anatomical record.

[66]  P. Rakic,et al.  Radial and horizontal deployment of clonally related cells in the primate neocortex: Relationship to distinct mitotic lineages , 1995, Neuron.

[67]  D. Schreyer,et al.  Topographic sequence of outgrowth of corticospinal axons in the rat: a study using retrograde axonal labeling with Fast blue. , 1988, Brain research.

[68]  B. Finlay.  Cell death and the creation of regional differences in neuronal numbers. , 1992, Journal of neurobiology.

[69]  G. Fishell,et al.  Dispersion of neural progenitors within the germinal zones of the forebrain , 1993, Nature.

[70]  M. Lavail,et al.  Rods and cones in the mouse retina. II. Autoradiographic analysis of cell generation using tritiated thymidine , 1979, The Journal of comparative neurology.

[71]  D. O'Leary,et al.  Do cortical areas emerge from a protocortex? , 1989, Trends in Neurosciences.

[72]  S. Kauffman.  Lengthening of the generation cycle during embryonic differentiation of the mouse neural tube. , 1968, Experimental cell research.

[73]  M. Oudega,et al.  Distribution of corticospinal motor neurons in the postnatal rat: Quantitative evidence for massive collateral elimination and modest cell death , 1994, The Journal of comparative neurology.

[74]  H. Killackey,et al.  The emergence of a discretely distributed pattern of corticospinal projection neurons. , 1984, Brain research.

[75]  P. Levitt,et al.  Cerebral cortical progenitors are fated to produce region-specific neuronal populations. , 1993, Cerebral cortex.

[76]  M. Roger,et al.  Development of spinal cord projections from neocortical transplants heterotopically placed in the neocortex of newborn hosts is highly dependent on the embryonic locus of origin of the graft , 1996, The Journal of comparative neurology.

[77]  D. Steindler,et al.  Abnormal glial and glycoconjugate dispositions in the somatosensory cortical barrel field of the early postnatal reeler mutant mouse. , 1987, Brain research.

[78]  P. Rakić,et al.  Mechanisms of cortical development: a view from mutations in mice. , 1978, Annual review of neuroscience.

[79]  K. Mikoshiba,et al.  Distribution and morphology of callosal commissural neurons within the motor cortex of normal and reeler mice , 1985, The Journal of comparative neurology.

[80]  R. Williams,et al.  The control of neuron number. , 1988, Annual review of neuroscience.

[81]  G. Fishell,et al.  Dispersion of neural progenitors within the germinal zones of the forebrain , 1993, Nature.

[82]  B. Nowak,et al.  Cycle times of the neural epithelial cells of various types of neuron in the rat. An autoradiographic study , 1974, The Journal of comparative neurology.

[83]  B. Stanfield,et al.  Fetal occipital cortical neurons transplanted to the rostral cortex can extend and maintain a pyramidal tract axon , 1985, Nature.

[84]  M. Miller,et al.  Development of Projection and Local Circuit Neurons in Neocortex , 1988 .

[85]  S. Mcconnell,et al.  Fates of visual cortical neurons in the ferret after isochronic and heterochronic transplantation , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[86]  M. Ishida,et al.  Cerebral cortical specification by early potential restriction of progenitor cells and later phenotype control of postmitotic neurons. , 1999, Development.

[87]  L. Thurlow,et al.  Cell lineage in the rat cerebral cortex: a study using retroviral-mediated gene transfer. , 1988, Development.

[88]  D. van der Kooy,et al.  The mouse mutation reeler causes increased adhesion within a subpopulation of early postmitotic cortical neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[89]  P. Levitt,et al.  Complex signaling responsible for molecular regionalization of the cerebral cortex. , 1999, Cerebral Cortex.

[90]  K. Mikoshiba,et al.  Distribution and morphology of corticospinal tract neurons in reeler mouse cortex by the retrograde HRP method , 1983, The Journal of comparative neurology.

[91]  M. Wassef,et al.  Role of thalamic axons in the expression of H-2Z1, a mouse somatosensory cortex specific marker. , 1999, Cerebral cortex.

[92]  R. Lund,et al.  Histogenesis of the superior colliculus of the albino rat: A tritiated thymidine study , 1979, Brain Research.

[93]  L. Schmued,et al.  Fluoro-gold: a new fluorescent retrograde axonal tracer with numerous unique properties , 1986, Brain Research.

[94]  D. van der Kooy,et al.  Neuronal lineages in chimeric mouse forebrain are segregated between compartments and in the rostrocaudal and radial planes. , 1990, Developmental biology.

[95]  B. Reese,et al.  Cell dispersion patterns in different cortical regions studied with an X-inactivated transgenic marker. , 1995, Development.

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

[97]  Y. Arimatsu,et al.  Early regional specification for a molecular neuronal phenotype in the rat neocortex. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[98]  P. Wahle,et al.  Areal Differences of NPY mRNA‐expressing Neurons are Established in the Late Postnatal Rat Visual Cortex In Vivo, but not in Organotypic Cultures , 1995, The European journal of neuroscience.

[99]  R. Douglas,et al.  A functional microcircuit for cat visual cortex. , 1991, The Journal of physiology.

[100]  R. Sidman,et al.  Time of origin of corresponding cell classes in the cerebral cortex of normal and reeler mutant mice: An autoradiographic analysis , 1973, The Journal of comparative neurology.

[101]  P. Clarke.  How inaccurate is the Abercrombie correction factor for cell counts? , 1992, Trends in Neurosciences.

[102]  E. Jones,et al.  Axon elimination in the developing corticospinal tract of the rat. , 1988, Brain research.