RECK in Neural Precursor Cells Plays a Critical Role in Mouse Forebrain Angiogenesis
RECK in Neural Precursor Cells Plays a Critical Role in Mouse Forebrain Angiogenesis
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DOI：
10.1016/j.isci.2019.08.009
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发表时间：
2019-08
期刊：
影响因子：
5.8
通讯作者：
Huiping Li;T. Miki;Glícia Maria de Almeida;Carina Hanashima;T. Matsuzaki;C. Kuo;Naoki Watanabe;M. Noda
中科院分区：
文献类型：
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作者：
Huiping Li;T. Miki;Glícia Maria de Almeida;Carina Hanashima;T. Matsuzaki;C. Kuo;Naoki Watanabe;M. Noda
先前发现神经前体细胞（NPC）中的RECK支持小鼠中Notch依赖的神经发生。另一方面，最近的研究表明，内皮细胞（EC）中的RECK参与了脑血管生成所必需的WNT 7触发的经典WNT信号传导。在这里，我们报告，RECK在NPC也是至关重要的脑血管生成。当Reckis在Foxg 1阳性NPC中失活时，小鼠在出生后不久就死于前脑出血，血管生成芽在外周停滞并形成异常聚集体，这让人想起EC选择性Reck敲除小鼠和Wnt 7a/b缺陷小鼠中的情况。氯化锂可明显抑制出血。在WNT 7产生细胞中的RECK增强报道细胞中的典型WNT信号传导的作用在混合培养物中是可检测的，但在条件培养基中不可检测。我们的研究结果表明，NPC表达的RECK有一个非细胞自主的功能，以促进前脑血管生成，通过接触依赖性增强的WNT信号在EC中，这意味着可能参与RECK在神经血管耦合。
RECK in neural precursor cells (NPCs) was previously found to support Notch-dependent neurogenesis in mice. On the other hand, recent studies implicate RECK in endothelial cells (ECs) in WNT7-triggered canonical WNT signaling essential for brain angiogenesis. Here we report that RECK in NPCs is also critical for brain angiogenesis. WhenReckis inactivated inFoxg1-positive NPCs, mice die shortly after birth with hemorrhage in the forebrain, with angiogenic sprouts stalling at the periphery and forming abnormal aggregates reminiscent of those in EC-selectiveReckknockout mice andWnt7a/b-deficient mice. The hemorrhage can be pharmacologically suppressed by lithium chloride. An effect of RECK in WNT7-producing cells to enhance canonical WNT-signaling in reporter cells is detectable in mixed culture but not with conditioned medium. Our findings suggest that NPC-expressed RECK has a non-cell-autonomous function to promote forebrain angiogenesis through contact-dependent enhancement of WNT signaling in ECs, implying possible involvement of RECK in neurovascular coupling.