Dentate granule cells in reeler mutants and VLDLR and ApoER2 knockout mice

Alexander Drakew, Thomas Deller, Bernd Heimrich, Carl Gebhardt, Domenico Del Turco, Albrecht Tielsch, Eckart Förster, Joachim Herz, Michael Frotscher

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

We have studied the organization and cellular differentiation of dentate granule cells and their axons, the mossy fibers, in reeler mutant mice lacking reelin and in mutants lacking the reelin receptors very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2). We show that granule cells in reeler mice do not form a densely packed granular layer, but are loosely distributed throughout the hilar region. Immunolabeling for calbindin and calretinin revealed that the sharp border between dentate granule cells and hilar mossy cells is completely lost in reeler mice. ApoER2/VLDLR double-knockout mice copy the reeler phenotype. Mice deficient only in VLDLR showed minor alterations of dentate organization; migration defects were more prominent in ApoER2 knockout mice. Tracing of the mossy fibers with Phaseolus vulgaris leukoagglutinin and calbindin immunolabeling revealed an irregular broad projection in reeler mice and ApoER2/VLDLR double knockouts, likely caused by the irregular wide distribution of granule cell somata. Mutants lacking only one of the lipoprotein receptors showed only minor changes in the mossy fiber projection. In all mutants, mossy fibers respected the CA3-CA1 border. Retrograde labeling with DiI showed that malpositioned granule cells also projected as normal to the CA3 region. These results indicate that (1) reelin signaling via ApoER2 and VLDLR is required for the normal positioning of dentate granule cells and (2) the reelin signaling pathway is not involved in pathfinding and target recognition of granule cell axons.

Original languageEnglish (US)
Pages (from-to)12-24
Number of pages13
JournalExperimental Neurology
Volume176
Issue number1
DOIs
Publication statusPublished - 2002

    Fingerprint

Keywords

  • Dentate gyrus
  • Hippocampal development
  • Mossy fibers
  • Mouse mutants
  • Neuronal migration
  • Reelin
  • Reelin receptor
  • Synaptogenesis

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Drakew, A., Deller, T., Heimrich, B., Gebhardt, C., Del Turco, D., Tielsch, A., ... Frotscher, M. (2002). Dentate granule cells in reeler mutants and VLDLR and ApoER2 knockout mice. Experimental Neurology, 176(1), 12-24. https://doi.org/10.1006/exnr.2002.7918