Angiogenesis within the developing mouse neural tube is dependent on sonic hedgehog signaling: possible roles of motor neurons
Angiogenesis within the developing mouse neural tube is dependent on sonic hedgehog signaling: possible roles of motor neurons
复制标题
DOI：
10.1111/j.1365-2443.2005.00861.x
复制
发表时间：
2005-06-01
期刊：
影响因子：
2.1
通讯作者：
Koshima, I
中科院分区：
文献类型：
--
作者：
Nagase, T;Nagase, M;Koshima, I
胚胎血管和神经系统的形态发生是紧密协调的，最近的研究表明，一些神经发生因子如Sonic hedgehog（Shh）也表现出血管发生潜力。发育中的小鼠神经管内的血管化依赖于从周围血管丛中出芽的血管。先前的研究暗示VEGF/Flk-1和血管生成素-1（Ang-1）/Tie-2信号传导作为在此过程中起作用的候选分子可能发挥作用。在胚胎（E）9.5和10.5天检测这些因子的基因表达，我们意外地发现VEGF和Ang-1都在腹侧神经管的运动神经元中表达。运动神经元确实位于浸润血管的附近，表明运动神经元参与发芽。为了证实这种可能性，我们抑制诱导的运动神经元在培养的小鼠胚胎环巴胺，Shh信号阻断剂。血管发芽显着受损的抑制Shh信号，连同几乎完全丧失的运动神经元。在环巴胺处理的胚胎中，神经管内Ang-1的表达显著降低，但VEGF的表达没有降低。这些结果表明，神经管血管生成依赖于Shh信号，并且至少部分地由Ang-1阳性运动神经元介导。
Embryonic morphogenesis of vascular and nervous systems is tightly coordinated, and recent studies revealed that some neurogenetic factors such as Sonic hedgehog (Shh) also exhibit angiogenetic potential. Vascularization within the developing mouse neural tube depends on vessel sprouting from the surrounding vascular plexus. Previous studies implicated possible roles of VEGF/Flk-1 and Angiopoietin-1(Ang-1)/Tie-2 signaling as candidate molecules functioning in this process. Examining gene expressions of these factors at embryonic day (E) 9.5 and 10.5, we unexpectedly found that both VEGF and Ang-1 were expressed in the motor neurons in the ventral neural tube. The motor neurons were indeed located in the close vicinity of the infiltrating vessels, suggesting involvement of motor neurons in the sprouting. To substantiate this possibility, we inhibited induction of the motor neurons in the cultured mouse embryos by cyclopamine, a Shh signaling blocker. The vessel sprouting was dramatically impaired by inhibition of Shh signaling, together with nearly complete loss of the motor neurons. Expression of Ang-1, but not VEGF, within the neural tube was remarkably reduced in the cyclopamine treated embryos. These results suggest that the neural tube angiogenesis is dependent on Shh signaling, and mediated, at least in part, by the Ang-1 positive motor neurons.