Peripheral nerve-derived CXCL12 and VEGF-A regulate the patterning of arterial vessel branching in developing limb skin.

Peripheral nerve-derived CXCL12 and VEGF-A regulate the patterning of arterial vessel branching in developing limb skin.
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DOI:
10.1016/j.devcel.2013.01.009
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发表时间:
2013-02-25
期刊:
影响因子:
11.8
通讯作者:
Mukouyama, Yoh-suke
Mukouyama, Yoh-suke
中科院分区:
生物学1区
文献类型:
--
作者:
Li, Wenling;Kohara, Hiroshi;Uchida, Yutaka;James, Jennifer M.;Soneji, Kosha;Cronshaw, Darran G.;Zou, Yong-Rui;Nagasawa, Takashi;Mukouyama, Yoh-suke

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在肢体皮肤发育过程中,周围神经提供了一个空间模板,控制动脉的分支模式和分化。我们以前的研究表明,神经来源的血管内皮生长因子-A是动脉分化所必需的,但不是神经血管排列所必需的。在这项研究中,我们证明了神经-血管排列依赖于CXCL12-CXCR4趋化因子信号的活性。CXCL12-CXCR4信号的遗传失活扰乱了神经-血管的排列,并取消了动脉的形成。进一步的体外分析使我们能够分离神经-血管排列和动脉形成,揭示神经来源的CXCL12刺激内皮细胞迁移,而神经来源的血管内皮生长因子-A负责动脉分化。这些发现表明,神经-CXCL12在一段距离内发挥作用,招募血管与神经对准,随后的动脉分化可能需要神经相关血管中的神经-血管内皮生长因子-A的局部作用。
In developing limb skin, peripheral nerves provide a spatial template that controls the branching pattern and differentiation of arteries. Our previous studies indicate that nerve-derived VEGF-A is required for arterial differentiation but not for nerve-vessel alignment. In this study, we demonstrate that nerve-vessel alignment depends on the activity of Cxcl12-Cxcr4 chemokine signaling. Genetic inactivation of Cxcl12-Cxcr4 signaling perturbs nerve-vessel alignment, and abolishes arteriogenesis. Further in vitro assays allow us to uncouple nerve-vessel alignment and arteriogenesis, revealing that nerve-derived Cxcl12 stimulates endothelial cell migration, while nerve-derived VEGF-A is responsible for arterial differentiation. These findings suggest a coordinated sequential action in which nerve-Cxcl12 functions over a distance to recruit vessels to align with nerves and subsequent arterial differentiation presumably requires a local-action of nerve-VEGF-A in the nerve-associated vessels.
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