Network of tangential pathways for neuronal migration in adult mammalian brain.

Cells in the brains of adult mammals continue to proliferate in the subventricular zone (SVZ) throughout the lateral wall of the lateral ventricle. Here we show, using whole mount dissections of this wall from adult mice, that the SVZ is organized as an extensive network of chains of neuronal precursors. These chains are immunopositive to the polysialylated form of NCAM, a molecule present at sites of plasticity, and TuJ1, an early neuronal marker. The majority of the chains are oriented along the rostrocaudal axis and many join the rostral migratory stream that terminates in the olfactory bulb. Using focal microinjections of DII and transplantation of SVZ cells carrying a neuron-specific reporter gene, we demonstrate that cells originating at different rostrocaudal levels of the SVZ migrate rostrally and reach the olfactory bulb where they differentiate into neurons. Our results reveal an extensive network of pathways for the tangential chain migration of neuronal precursors throughout the lateral wall of the lateral ventricle in the adult mammalian brain.

[1]  U. Rutishauser,et al.  A Septum-Derived Chemorepulsive Factor for Migrating Olfactory Interneuron Precursors , 1996, Neuron.

[2]  A. Frankfurter,et al.  Initial tract formation in the mouse brain , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  J. Altman.  Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb , 1969, The Journal of comparative neurology.

[4]  S. Levison,et al.  Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain , 1993, Neuron.

[5]  C. Lois,et al.  Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[6]  T. Magnuson,et al.  The Role of Polysialic Acid in Migration of Olfactory Bulb Interneuron Precursors in the Subventricular Zone , 1996, Neuron.

[7]  A. Frankfurter,et al.  The expression and posttranslational modification of a neuron-specific beta-tubulin isotype during chick embryogenesis. , 1990, Cell motility and the cytoskeleton.

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

[9]  I. Smart.  The subependymal layer of the mouse brain and its cell production as shown by radioautography after thymidine‐H3 injection , 1961 .

[10]  T. Seki,et al.  Distribution and possible roles of the highly polysialylated neural cell adhesion molecule (NCAM-H) in the developing and adult central nervous system , 1993, Neuroscience Research.

[11]  D. van der Kooy,et al.  Postmitotic death is the fate of constitutively proliferating cells in the subependymal layer of the adult mouse brain , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[13]  S. Goldman,et al.  Brain-derived neurotrophic factor promotes the survival of neurons arising from the adult rat forebrain subependymal zone. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[14]  C. Lois,et al.  Embryonic (PSA) N‐CAM reveals chains of migrationg neuroblasts between the lateral ventricle and the olfactory bulb of adult mice , 1995, The Journal of comparative neurology.

[15]  T. Magnuson,et al.  Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces distinct defects in the central nervous system , 1993, Neuron.

[16]  C. P. Leblond,et al.  The subependymal layer and neighboring region in the brain of the young rat , 1972, The Journal of comparative neurology.

[17]  F. Gage,et al.  Isolation, characterization, and use of stem cells from the CNS. , 1995, Annual review of neuroscience.

[18]  Maria B. Luskin,et al.  Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone , 1993, Neuron.

[19]  L. Bonfanti,et al.  Expression of polysialylated neural cell adhesion molecule by proliferating cells in the subependymal layer of the adult rat, in its rostral extension and in the olfactory bulb , 1994, Neuroscience.

[20]  J. Sanes,et al.  Migratory paths of neurons and glia in the embryonic chick spinal cord , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  C. Lois,et al.  Neuronal stem cells in the brain of adult vertebrates , 1995, Stem cells.

[22]  M. Nerenberg,et al.  Transgenic mice expressing β-galactosidase in mature neurons under neuron-specific enolase promoter control , 1990, Neuron.

[23]  J. Maruniak,et al.  Neurogenesis persists in the subependymal layer of the adult mouse brain , 1993, Neuroscience Letters.

[24]  S. Mcconnell,et al.  Diverse migratory pathways in the developing cerebral cortex. , 1992, Science.

[25]  G. Rougon,et al.  A monoclonal antibody against meningococcus group B polysaccharides distinguishes embryonic from adult N-CAM , 1986, The Journal of cell biology.

[26]  Brent A. Reynolds,et al.  Neural stem cells in the adult mammalian forebrain: A relatively quiescent subpopulation of subependymal cells , 1994, Neuron.

[27]  D. Steindler,et al.  Young neurons from the adult subependymal zone proliferate and migrate along an astrocyte, extracellular matrix‐rich pathway , 1996, Glia.

[28]  Arturo Alvarez-Buylla,et al.  Chain Migration of Neuronal Precursors , 1996, Science.

[29]  K. Rajewsky,et al.  Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning , 1994, Nature.

[30]  T. Magnuson,et al.  N-CAM mutation inhibits tangential neuronal migration and is phenocopied by enzymatic removal of polysialic acid , 1994, Neuron.

[31]  K. Kishi.  Golgi studies on the development of granule cells of the rat olfactory bulb with reference to migration in the subependymal layer , 1987, The Journal of comparative neurology.

[32]  W. Blakemore,et al.  The subependymal plate and associated ependyma in the dog. An ultrastructural study , 1972, Journal of neurocytology.

[33]  C. Lois,et al.  Long-distance neuronal migration in the adult mammalian brain. , 1994, Science.

[34]  M B Luskin,et al.  Expression of neuron-specific tubulin defines a novel population in the proliferative layers of the developing telencephalon , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  S. Breen,et al.  Radial mosaicism and tangential cell dispersion both contribute to mouse neocortical development , 1993, Nature.

[36]  C. Cepko,et al.  Generation and migration of cells in the developing striatum , 1992, Neuron.