Takahashi Teruaki, Takase Yuta, Yoshino Takashi, Saito Daisuke, Tadokoro Ryosuke, Takahashi Yoshiko
Department of Zoology, Graduate School of Science, Kyoto University, Kyoto, Japan; Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
Department of Zoology, Graduate School of Science, Kyoto University, Kyoto, Japan.
PLoS One. 2015 Jan 13;10(1):e0116119. doi: 10.1371/journal.pone.0116119. eCollection 2015.
Blood vessels in the central nervous system supply a considerable amount of oxygen via intricate vascular networks. We studied how the initial vasculature of the spinal cord is formed in avian (chicken and quail) embryos. Vascular formation in the spinal cord starts by the ingression of intra-neural vascular plexus (INVP) from the peri-neural vascular plexus (PNVP) that envelops the neural tube. At the ventral region of the PNVP, the INVP grows dorsally in the neural tube, and we observed that these vessels followed the defined path at the interface between the medially positioned and undifferentiated neural progenitor zone and the laterally positioned differentiated zone. When the interface between these two zones was experimentally displaced, INVP faithfully followed a newly formed interface, suggesting that the growth path of the INVP is determined by surrounding neural cells. The progenitor zone expressed mRNA of vascular endothelial growth factor-A whereas its receptor VEGFR2 and FLT-1 (VEGFR1), a decoy for VEGF, were expressed in INVP. By manipulating the neural tube with either VEGF or the soluble form of FLT-1, we found that INVP grew in a VEGF-dependent manner, where VEGF signals appear to be fine-tuned by counteractions with anti-angiogenic activities including FLT-1 and possibly semaphorins. These results suggest that the stereotypic patterning of early INVP is achieved by interactions between these vessels and their surrounding neural cells, where VEGF and its antagonists play important roles.
中枢神经系统中的血管通过复杂的血管网络供应大量氧气。我们研究了禽类（鸡和鹌鹑）胚胎中脊髓初始脉管系统的形成方式。脊髓中的血管形成始于神经内血管丛（INVP）从包裹神经管的神经周血管丛（PNVP）侵入。在PNVP的腹侧区域，INVP在神经管中向背侧生长，我们观察到这些血管沿着内侧定位的未分化神经祖细胞区和外侧定位的分化区之间的界面处的特定路径生长。当这两个区域之间的界面通过实验移位时，INVP忠实地跟随新形成的界面，这表明INVP的生长路径由周围的神经细胞决定。祖细胞区表达血管内皮生长因子-A的mRNA，而其受体VEGFR2和FLT-1（VEGFR1，一种VEGF诱饵）在INVP中表达。通过用VEGF或可溶性形式的FLT-1处理神经管，我们发现INVP以VEGF依赖的方式生长，其中VEGF信号似乎通过与包括FLT-1以及可能的信号素在内的抗血管生成活性的相互作用而得到微调。这些结果表明，早期INVP的定型模式是通过这些血管与其周围神经细胞之间的相互作用实现的，其中VEGF及其拮抗剂发挥着重要作用。
