The angiopoietin-Tie2 pathway regulates Purkinje cell dendritic morphogenesis in a cell-autonomous manner.
The angiopoietin-Tie2 pathway regulates Purkinje cell dendritic morphogenesis in a cell-autonomous manner.
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DOI：
10.1016/j.celrep.2021.109522
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发表时间：
2021-08-17
期刊：
影响因子：
8.8
通讯作者：
de Almodovar, Carmen Ruiz
中科院分区：
文献类型：
--
作者：
Luck, Robert;Karakatsani, Andromachi;Shah, Bhavin;Schermann, Geza;Adler, Heike;Kupke, Janina;Tisch, Nathalie;Jeong, Hyun-Woo;Back, Michaela Kerstin;Hetsch, Florian;D'Errico, Anna;De Palma, Michele;Wiedtke, Ellen;Grimm, Dirk;Acker-Palmer, Amparo;von Engelhardt, Jakob;Adams, Ralf H.;Augustin, Hellmut G.;de Almodovar, Carmen Ruiz
神经-血管通讯对于同步中枢神经系统发育至关重要。在这里，我们确定血管生成素/Tie 2作为参与调节浦肯野细胞（PC）的树突状形态发生的神经血管信号轴。我们发现，在发展中的小脑Tie 2表达不仅限于血管，但它也存在于PC。其配体血管生成素-1（Ang 1）和血管生成素-2（Ang 2）分别在神经细胞和内皮细胞中表达。Tie 2的PC特异性缺失导致树突状分支减少，这在神经特异性Ang 1敲除和Ang 2全敲除小鼠中重现。从机制上讲，RNA测序显示Tie 2缺陷的PC存在参与细胞骨架组织、树突形成、生长和分支的多个基因的基因表达的改变。在功能上，PC中Tie 2缺失的小鼠存在PC网络功能的改变。总之，我们的数据表明，Ang/Tie 2信号作为神经细胞，EC和PC之间的细胞间通讯的介质，需要适当的PC树突状形态和功能。Luck等人描述了一种调节浦肯野细胞树突形态发生的机制。他们表明Tie 2信号传导在浦肯野细胞中以细胞自主的方式起作用。配体Ang 1和Ang 2分别在神经细胞和内皮细胞中表达。该通路是适当的树突形态发生和神经元功能所必需的。
Neuro-vascular communication is essential to synchronize central nervous system development. Here, we identify angiopoietin/Tie2 as a neuro-vascular signaling axis involved in regulating dendritic morphogenesis of Purkinje cells (PCs). We show that in the developing cerebellum Tie2 expression is not restricted to blood vessels, but it is also present in PCs. Its ligands angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) are expressed in neural cells and endothelial cells (ECs), respectively. PC-specific deletion of Tie2 results in reduced dendritic arborization, which is recapitulated in neural-specific Ang1-knockout and Ang2 full-knockout mice. Mechanistically, RNA sequencing reveals that Tie2-deficient PCs present alterations in gene expression of multiple genes involved in cytoskeleton organization, dendritic formation, growth, and branching. Functionally, mice with deletion of Tie2 in PCs present alterations in PC network functionality. Altogether, our data propose Ang/Tie2 signaling as a mediator of intercellular communication between neural cells, ECs, and PCs, required for proper PC dendritic morphogenesis and function. Luck et al. describe a mechanism regulating Purkinje cell dendritic morphogenesis. They show that Tie2 signaling acts in a cell-autonomous manner in Purkinje cells. The ligands, Ang1 and Ang2, are expressed in neural and endothelial cells, respectively. This pathway is required for proper dendritic morphogenesis and neuronal functionality.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
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通讯作者：
Huber W
影响因子：
11.8
作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
Brindle NP
DOI：
10.1242/dev.081315
发表时间：
2012-09
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Fujishima K;Horie R;Mochizuki A;Kengaku M
通讯作者：
Kengaku M
DOI：
10.1152/ajplung.2001.281.3.l582
发表时间：
2001-09-01
影响因子：
4.9
作者：
Abdulmalek, K;Ashur, F;Hussain, SNA
通讯作者：
Hussain, SNA