Specific glial populations regulate hippocampal morphogenesis

Guy Barry, Michael Piper, Charlotta Lindwall, Randal Moldrich, Sharon Mason, Erica Little, Anindita Sarkar, Shubha Tole, Richard M. Gronostajski, Linda J. Richardse

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

The hippocampus plays an integral role in spatial navigation, learning and memory, and is a major site for adult neurogenesis. Critical to these functions is the proper organization of the hippocampus during development. Radial glia are known to regulate hippocampal formation, but their precise function in this process is yet to be defined. We find that in Nuclear Factor I b (Nfib)-deficient mice, a subpopulation of glia from the ammonic neuroepithelium of the hippocampus fail to develop. This results in severe morphological defects, including a failure of the hippocampal fissure, and subsequently the dentate gyrus, to form. As in wild-type mice, immature nestin-positive glia, which encompass all types of radial glia, populate the hippocampus in Nfib-deficient mice at embryonic day 15. However, these fail to mature into GLAST- and GFAP-positive glia, and the supragranular glial bundle is absent. In contrast, the fimbrial glial bundle forms, but alone is insufficient for proper hippocampal morphogenesis. Dentate granule neurons are present in the mutant hippocampus but their migration is aberrant, likely resulting from the lack of the complete radial glial scaffold usually provided by both glial bundles. These data demonstrate a role for Nfib in hippocampal fissure and dentate gyrus formation, and that distinct glial bundles are critical for correct hippocampal morphogenesis.

Original languageEnglish
Pages (from-to)12328-12340
Number of pages13
JournalJournal of Neuroscience
Volume28
Issue number47
DOIs
StatePublished - Nov 19 2008

Keywords

  • Dentate gyrus
  • Glial development
  • Gliogenesis
  • Hippocampal fissure
  • Neuronal migration
  • Supragranular bundle

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