Deletion of collapsin response mediator protein 4 results in abnormal layer thickness and elongation of mitral cell apical dendrites in the neonatal olfactory bulb
Deletion of collapsin response mediator protein 4 results in abnormal layer thickness and elongation of mitral cell apical dendrites in the neonatal olfactory bulb
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DOI：
10.1111/joa.12434
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发表时间：
2016-05
影响因子：
2.4
通讯作者：
A. Tsutiya;Hikaru Watanabe;Yui Nakano;M. Nishihara;Y. Goshima;R. Ohtani-Kaneko
中科院分区：
文献类型：
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作者：
A. Tsutiya;Hikaru Watanabe;Yui Nakano;M. Nishihara;Y. Goshima;R. Ohtani-Kaneko
塌陷反应介质蛋白4 （CRMP4）是CRMP家族的一员，参与了精神分裂症和自闭症等神经发育障碍的发病机制。在这里，我们首先比较了野生型（WT）和CRMP4敲除（KO）小鼠嗅球的层厚度。与WTs相比，CRMP4‐KO小鼠在出生后第0天（PD0）的二尖瓣细胞层（MCL）明显变薄，而外网状层（EPL）明显变厚。而PD14则使层厚差异消失。在CRMP4‐KO新生儿中，MCL中未发现凋亡细胞，用特定标记物（即Tbx21抗体）鉴定的二尖瓣细胞（MCs）数量未发生变化。然而，DiI‐追踪显示，CRMP4‐KO新生儿的二尖瓣细胞顶端树突长度大于WTs。此外，WT小鼠在PD0时MCL中CRMP4 mRNA的表达最丰富，随后表达减少。这些结果表明CRMP4有助于枝晶伸长。我们的体外研究表明，CRMP4的缺失或敲低导致MAP2阳性神经突的生长增强，而CRMP4的过表达则会降低其生长，这表明CRMP4作为树突伸长抑制因子的新作用。总的来说，我们的数据表明，CRMP4的破坏通过增强二尖瓣细胞顶端树突的生长，产生了EPL厚度的暂时改变，EPL厚度主要由二尖瓣细胞顶端树突组成。
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.