Extracellular matrix composition affects outgrowth of dendrites and dendritic spines on cortical neurons.
Extracellular matrix composition affects outgrowth of dendrites and dendritic spines on cortical neurons.
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DOI：
10.3389/fncel.2023.1177663
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发表时间：
2023
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
神经组织中细胞外基质（ECM）的组成在控制神经元生长和突触发育中起着重要作用。ECM的蛋白质和糖胺聚糖成分的变化发生在组织损伤中，并可能影响神经元的生长。为了研究神经元对纤维连接蛋白（FN）（伤口ECM的主要成分）改变的反应，我们在细胞来源的脱细胞基质上培养皮质神经元，这些基质由野生型FN （FN+/+）或突变型FN （FNΔ/+）组成，其中通过CRISPR-Cas 9基因编辑删除了III13肝素结合位点。突变体FN最显著的影响是减少了树突的生长。突变型FNΔ/+-胶原（COL）基质上的树突不仅比野生型（FN+/+-COL）基质短，而且在FNΔ/+-COL基质上，每个神经元的树突数和树突棘数以及棘密度也显著降低。质谱和免疫染色鉴定突变基质中tenascin-C （TN-C）水平降低。TN-C是一种ECM蛋白，与FN的III13位点结合，调节细胞-基质相互作用，并与树突发育有关。我们提出TN-C与创面基质中FN的结合在受损神经组织修复过程中支持树突和脊柱的发育。总的来说，这些结果表明，ECM成分的变化可以显著影响神经突的发育，并支持ECM微环境控制神经元形态和连通性的观点。
The composition of the extracellular matrix (ECM) in nervous tissue plays an important role in controlling neuronal outgrowth and synapse development. Changes in both protein and glycosaminoglycan components of the ECM occur with tissue injury and may affect neuron growth. To investigate neuron responses to alterations in fibronectin (FN), a major component of the wound ECM, we grew cortical neurons on cell-derived decellularized matrices composed of wild type FN (FN+/+) or of a mutant form of FN (FNΔ/+) from which the III13 heparin-binding site had been deleted by CRISPR-Cas 9 gene editing. The most significant effect of the mutant FN was a reduction in dendrite outgrowth. Not only were dendrites shorter on mutant FNΔ/+-collagen (COL) matrix than on wild type (FN+/+-COL) matrix, but the number of dendrites and dendritic spines per neuron and the spine densities were also dramatically reduced on FNΔ/+-COL matrices. Mass spectrometry and immunostaining identified a reduction in tenascin-C (TN-C) levels in the mutant matrix. TN-C is an ECM protein that binds to the III13 site of FN and modulates cell-matrix interactions and has been linked to dendrite development. We propose that TN-C binding to FN in the wound matrix supports dendrite and spine development during repair of damaged neural tissue. Overall, these results show that changes in ECM composition can dramatically affect elaboration of neurites and support the idea that the ECM microenvironment controls neuron morphology and connectivity.
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影响因子：
5.3
作者：
Kurshan, Peri T.;Phan, Allan Q.;Shen, Kang
通讯作者：
Shen, Kang
影响因子：
5.7
作者：
Dent EW;Merriam EB;Hu X
通讯作者：
Hu X
DOI：
10.1016/j.biocel.2003.12.002
发表时间：
2004-06-01
影响因子：
4
作者：
Chiquet-Ehrismann, R
通讯作者：
Chiquet-Ehrismann, R
DOI：
10.1073/pnas.051614698
发表时间：
2001-03-13
影响因子：
11.1
作者：
Liu, WS;Pesold, C;Costa, E
通讯作者：
Costa, E
影响因子：
5.3
作者：
Kjell, Jacob;Goetz, Magdalena
通讯作者：
Goetz, Magdalena