Expression of constitutively active p21H-rasVa112 in postmitotic pyramidal neurons results in increased dendritic size and complexity

Expression of constitutively active p21H-rasVa112 in postmitotic pyramidal neurons results in increased dendritic size and complexity
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DOI:
10.1002/cne.10915
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发表时间:
2003-12-01
影响因子:
2.5
通讯作者:
Gärtner, U
Gärtner, U
中科院分区:
医学3区
文献类型:
--
作者:
Alpár, A;Palm, K;Gärtner, U

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小G蛋白p21Ras是传递神经营养作用的关键分子开关,对神经系统的正常功能和可塑性是必不可少的。本研究探讨了p21Ras对活体神经元的形态发生作用。对p21H-RAS(Val12)转基因小鼠初级体感皮层II/III层和Vb层锥体细胞的形态变化进行了分析。用生物素化的葡聚糖胺逆行标记锥体细胞,然后用神经荧光素追踪。与野生型小鼠相比,转基因动物在第II/III层的近端和中间节段以及第V层的更远端节段的树突基表面积和体积均显著增加,且两层树突的主干和斜枝的近节段的表面积和体积均增大。对基底和顶端树突的Sholl分析表明,V层神经元的树突复杂性显著增加。在转基因群体中,树突基的大小与神经元胞体的大小呈正相关,表明p21H-RAS(Val12)的促生长作用平行地影响两个细胞室。然而,在野生型和转基因群体中,树突表面与树梢数量和树枝茎直径相关,表明这些关系在树突形态上代表了相当保守的设计原则。这些数据表明,依赖于p21Ras的信号在树突形态的最终分化和维持中起着重要作用。(C)2003年Wiley-Liss,Inc.
The small G protein p21Ras is a critical molecular switch for relaying neurotrophic actions and is essential for normal functioning and plasticity of the nervous system. In this study, the morphogenetic effects of p21Ras were investigated on neurons in vivo. Morphological changes of layers II/III and Vb commissural pyramidal neurons of the primary somatosensory cortex were analyzed in transgenic mice expressing permanently active p21H-Ras(Val12) in postmitotic neurons. Pyramidal cells were retrogradely labelled with biotinylated dextran amine and subsequently traced using Neurolucida. Compared with wild-type mice, transgenic animals showed a significant increase in the surface area and volume of basal dendrites on the proximal and intermediate segments in layers II/III and on further distal segments in layer V. In addition, the surface area and volume of the trunk and of the proximal segments of oblique branches of apical dendrites were enlarged in both layers. Sholl analyses of basal and apical dendrites showed a significant increase in dendritic complexity of layer V neurons. A positive correlation was observed between the size of the basal dendrite and the neuronal soma size in the transgenic population, indicating that growth-promoting effects of p21H-Ras(Val12) affect both cellular compartments in parallel. However, the dendritic surface correlated with the number of tips and dendritic stem diameter in both wild-type and transgenic populations, demonstrating that these relations represent rather conservative design principles in dendritic morphology. The data presented here suggest an important role of p21Ras-dependent signaling in the final differentiation and maintenance of dendritic morphology. (C) 2003 Wiley-Liss, Inc.