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解偶联树突生长与模式形成:N-甲基-D-天冬氨酸受体2B的单细胞基因敲除分析

Uncoupling dendrite growth and patterning: single-cell knockout analysis of NMDA receptor 2B.

作者信息

Espinosa J Sebastian, Wheeler Damian G, Tsien Richard W, Luo Liqun

机构信息

Department of Biology, Stanford University, Stanford, CA 94305, USA.

出版信息

Neuron. 2009 Apr 30;62(2):205-17. doi: 10.1016/j.neuron.2009.03.006.

Abstract

N-methyl-D-aspartate receptors (NMDARs) play important functions in neural development. NR2B is the predominant NR2 subunit of NMDAR in the developing brain. Here we use mosaic analysis with double markers (MADM) to knock out NR2B in isolated single cells and analyze its cell-autonomous function in dendrite development. NR2B mutant dentate gyrus granule cells (dGCs) and barrel cortex layer 4 spiny stellate cells (bSCs) have similar dendritic growth rates, total length, and branch number as control cells. However, mutant dGCs maintain supernumerary primary dendrites resulting from a pruning defect. Furthermore, while control bSCs restrict dendritic growth to a single barrel, mutant bSCs maintain dendritic growth in multiple barrels. Thus, NR2B functions cell autonomously to regulate dendrite patterning to ensure that sensory information is properly represented in the cortex. Our study also indicates that molecular mechanisms that regulate activity-dependent dendrite patterning can be separated from those that control general dendrite growth and branching.

摘要

N-甲基-D-天冬氨酸受体(NMDARs)在神经发育中发挥着重要作用。NR2B是发育中大脑中NMDAR的主要NR2亚基。在此,我们使用双标记镶嵌分析(MADM)在分离的单细胞中敲除NR2B,并分析其在树突发育中的细胞自主功能。NR2B突变型齿状回颗粒细胞(dGCs)和桶状皮质第4层棘状星状细胞(bSCs)与对照细胞具有相似的树突生长速率、总长度和分支数量。然而,突变型dGCs由于修剪缺陷而保留了多余的初级树突。此外,虽然对照bSCs将树突生长限制在单个桶状区域内,但突变型bSCs在多个桶状区域内维持树突生长。因此,NR2B通过细胞自主功能调节树突模式,以确保感觉信息在皮质中得到正确呈现。我们的研究还表明,调节活动依赖性树突模式的分子机制可以与控制一般树突生长和分支的机制分开。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b6e/2788338/c3db08ab27a9/nihms115206f1.jpg

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