Deletion of collapsin response mediator protein 4 results in abnormal layer thickness and elongation of mitral cell apical dendrites in the neonatal olfactory bulb

J Anat. 2016 May;228(5):792-804. doi: 10.1111/joa.12434. Epub 2016 Jan 6.

Abstract

Collapsin response mediator protein 4 (CRMP4), a member of the CRMP family, is involved in the pathogenesis of neurodevelopmental disorders such as schizophrenia and autism. Here, we first compared layer thickness of the olfactory bulb between wild-type (WT) and CRMP4-knockout (KO) mice. The mitral cell layer (MCL) was significantly thinner, whereas the external plexiform layer (EPL) was significantly thicker in CRMP4-KO mice at postnatal day 0 (PD0) compared with WTs. However, differences in layer thickness disappeared by PD14. No apoptotic cells were found in the MCL, and the number of mitral cells (MCs) identified with a specific marker (i.e. Tbx21 antibody) did not change in CRMP4-KO neonates. However, DiI-tracing showed that the length of mitral cell apical dendrites was greater in CRMP4-KO neonates than in WTs. In addition, expression of CRMP4 mRNA in WT mice was most abundant in the MCL at PD0 and decreased afterward. These results suggest that CRMP4 contributes to dendritic elongation. Our in vitro studies showed that deletion or knockdown of CRMP4 resulted in enhanced growth of MAP2-positive neurites, whereas overexpression of CRMP4 reduced their growth, suggesting a new role for CRMP4 as a suppressor of dendritic elongation. Overall, our data suggest that disruption of CRMP4 produces a temporary alteration in EPL thickness, which is constituted mainly of mitral cell apical dendrites, through the enhanced growth of these dendrites.

Keywords: CRMP4-knockout mice; brain development; dendrite development; neurodevelopmental disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Dendrites / pathology*
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / metabolism*
  • Olfactory Bulb / pathology*

Substances

  • Crmp-4 protein, mouse
  • Nerve Tissue Proteins

Associated data

  • GENBANK/AF389425.1