Increased proximal bifurcation of CA1 pyramidal apical dendrites in sema3A mutant mice

Increased proximal bifurcation of CA1 pyramidal apical dendrites in sema3A mutant mice
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DOI:
10.1002/cne.22125
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发表时间:
2009-10
影响因子:
2.5
通讯作者:
F. Nakamura;Kozue Ugajin;N. Yamashita;Takako Okada;Yutaka Uchida;M. Taniguchi;T. Ohshima;Y. Goshima
F. Nakamura;Kozue Ugajin;N. Yamashita;Takako Okada;Yutaka Uchida;M. Taniguchi;T. Ohshima;Y. Goshima
中科院分区:
医学3区
文献类型:
--
作者:
F. Nakamura;Kozue Ugajin;N. Yamashita;Takako Okada;Yutaka Uchida;M. Taniguchi;T. Ohshima;Y. Goshima

文献摘要

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Semaphorin-3A(Sema 3A)是一种有吸引力的皮质顶树突导向分子。为了阐明Sema 3A在海马树突形成中的作用,我们研究了Sema 3A在围产期海马结构中的表达模式,并分析了年轻成年sema 3A突变小鼠大脑的海马树突。Sema 3A蛋白在顶树突生长初期主要表达于海马板和内缘区。神经纤毛蛋白-1和丛蛋白-A,Sema 3A的受体成分,也位于相同的区域。高尔基体浸渍法显示,在野生型小鼠海马CA 1区锥体神经元的90%以上延长一个单一的干或顶端干在放射层分叉。7%的锥体神经元在锥体层或锥体层与放射层交界处出现顶干近端分叉。在sema 3A突变小鼠,近端分叉的顶树突增加到32%,而单一的顶树突锥体神经元减少。我们将sema 3A突变小鼠的这种表型称为“近端分叉”。在分离培养系统中,大约一半的野生型小鼠海马神经元类似于锥体神经元,具有长,厚,锥形树突。相比之下,来自sema 3A突变体的神经元中只有30%表现出锥体样形态。CA 1锥体神经元的近端分叉也在p35突变小鼠中增加,p35是细胞周期蛋白依赖性激酶5(Cdk 5)的激活剂。因此,Sema 3A可能通过激活p35/Cdk 5促进CA 1顶树突的初始生长,这可能反过来又是海马发育的信号。J. Comp.神经元516:360-375,2009.© 2009 Wiley利斯公司
Semaphorin‐3A (Sema3A) is an attractive guidance molecule for cortical apical dendrites. To elucidate the role of Sema3A in hippocampal dendritic formation, we examined the Sema3A expression pattern in the perinatal hippocampal formation and analyzed hippocampal dendrites of the brains from young adult sema3A mutant mice. Sema3A protein was predominantly expressed in the hippocampal plate and the inner marginal zone at the initial period of apical dendritic growth. Neuropilin‐1 and plexin‐A, the receptor components for Sema3A, were also localized in the same regions. The Golgi impregnation method revealed that in wildtype mice more than 90% of hippocampal CA1 pyramidal neurons extended a single trunk or apical trunks bifurcated in stratum radiatum. Seven percent of the pyramidal neurons showed proximal bifurcation of apical trunks in stratum pyramidale or at the border of the stratum pyramidale and stratum radiatum. In sema3A mutant mice, proximally bifurcated apical dendrites were increased to 32%, while the single apical dendritic pyramidal neurons were decreased. We designate this phenotype in sema3A mutant mice as “proximal bifurcation.” In the dissociated culture system, approximately half of the hippocampal neurons from wildtype mice resembled pyramidal neurons, which possess a long, thick, and tapered dendrite. In contrast, only 30% of the neurons from sema3A mutants exhibited pyramidal‐like morphology. Proximal bifurcation of CA1 pyramidal neurons was also increased in the mutant mice of p35, an activator of cyclin‐dependent kinase 5 (Cdk5). Thus, Sema3A may facilitate the initial growth of CA1 apical dendrites via the activation of p35/Cdk5, which may in turn signal hippocampal development. J. Comp. Neurol. 516:360–375, 2009. © 2009 Wiley‐Liss, Inc.