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Deletion of collapsin response mediator protein 4 results in abnormal layer thickness and elongation of mitral cell apical dendrites in the neonatal olfactory bulb
Author(s) -
Tsutiya Atsuhiro,
Watanabe Hikaru,
Nakano Yui,
Nishihara Masugi,
Goshima Yoshio,
OhtaniKaneko Ritsuko
Publication year - 2016
Publication title -
journal of anatomy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 118
eISSN - 1469-7580
pISSN - 0021-8782
DOI - 10.1111/joa.12434
Subject(s) - olfactory bulb , neurite , biology , microbiology and biotechnology , medicine , in vitro , endocrinology , central nervous system , biochemistry
Collapsin response mediator protein 4 ( CRMP 4), 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 CRMP 4 ‐knockout ( KO ) mice. The mitral cell layer ( MCL ) was significantly thinner, whereas the external plexiform layer ( EPL ) was significantly thicker in CRMP 4 ‐ KO mice at postnatal day 0 ( PD 0) compared with WT s. However, differences in layer thickness disappeared by PD 14. No apoptotic cells were found in the MCL , and the number of mitral cells ( MC s) identified with a specific marker (i.e. Tbx21 antibody) did not change in CRMP 4 ‐ KO neonates. However, DiI‐tracing showed that the length of mitral cell apical dendrites was greater in CRMP 4 ‐ KO neonates than in WT s. In addition, expression of CRMP 4 mRNA in WT mice was most abundant in the MCL at PD 0 and decreased afterward. These results suggest that CRMP 4 contributes to dendritic elongation. Our in vitro studies showed that deletion or knockdown of CRMP 4 resulted in enhanced growth of MAP 2‐positive neurites, whereas overexpression of CRMP 4 reduced their growth, suggesting a new role for CRMP 4 as a suppressor of dendritic elongation. Overall, our data suggest that disruption of CRMP 4 produces a temporary alteration in EPL thickness, which is constituted mainly of mitral cell apical dendrites, through the enhanced growth of these dendrites.