title: Deletion of collapsin response mediator protein 4 results in abnormal layer thickness and elongation of mitral cell apical dendrites in the neonatal olfactory bulb.
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.
authors.affiliation: Graduate School of Life Sciences, Toyo University, Oura, Gunma, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Tsutiya
authors.affiliation: Graduate School of Life Sciences, Toyo University, Oura, Gunma, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Graduate School of Life Sciences, Toyo University, Oura, Gunma, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Masugi
authors.initials: M
authors.lastname: Nishihara
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanazawa Ward, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.affiliation: Graduate School of Life Sciences, Toyo University, Oura, Gunma, Japan.|Bio-Nano Electronic Research Centre, Toyo University, Kawagoe, Saitama, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Ohtani-Kaneko
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003712:Dendrites / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D009830:Olfactory Bulb / Q000473:pathology*
chemical_list: C526904:Dpysl3 protein, mouse; D009419:Nerve Tissue Proteins
keywords: CRMP4-knockout mice; brain development; dendrite development; neurodevelopmental disorders