Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain

Proc Natl Acad Sci U S A. 2015 Jul 28;112(30):9484-9. doi: 10.1073/pnas.1508545112. Epub 2015 Jul 13.

Abstract

In a classic model of mammalian brain formation, precursors of principal glutamatergic neurons migrate radially along radial glia fibers whereas GABAergic interneuron precursors migrate tangentially. These migration modes have significant implications for brain function. Here we used clonal lineage tracing of active radial glia-like neural stem cells in the adult mouse dentate gyrus and made the surprising discovery that proliferating neuronal precursors of glutamatergic granule neurons exhibit significant tangential migration along blood vessels, followed by limited radial migration. Genetic birthdating and morphological and molecular analyses pinpointed the neuroblast stage as the main developmental window when tangential migration occurs. We also developed a partial "whole-mount" dentate gyrus preparation and observed a dense plexus of capillaries, with which only neuroblasts, among the entire population of progenitors, are directly associated. Together, these results provide insight into neuronal migration in the adult mammalian nervous system.

Keywords: adult neurogenesis; hippocampus; lineage tracing; migration; vascular niche.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain Mapping / methods
  • Cell Movement
  • Dentate Gyrus / physiology*
  • Female
  • Glutamine / chemistry*
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / physiology
  • Imaging, Three-Dimensional
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Models, Neurological
  • Neural Stem Cells / cytology
  • Neurogenesis / physiology*
  • Neurons / cytology
  • Neurons / physiology*

Substances

  • Glutamine
  • Green Fluorescent Proteins