Molecular Medicine Program, 15 N 2030 East, Room 4140, University of Utah, Salt Lake City, UT 84112, USA.
Development. 2011 Sep;138(17):3847-57. doi: 10.1242/dev.068403.
The neural and vascular systems share common guidance cues that have direct and independent signaling effects on nerves and endothelial cells. Here, we show that zebrafish Netrin 1a directs Dcc-mediated axon guidance of motoneurons and that this neural guidance function is essential for lymphangiogenesis. Specifically, Netrin 1a secreted by the muscle pioneers at the horizontal myoseptum (HMS) is required for the sprouting of dcc-expressing rostral primary motoneuron (RoP) axons and neighboring axons along the HMS, adjacent to the future trajectory of the parachordal chain (PAC). These axons are required for the formation of the PAC and, subsequently, the thoracic duct. The failure to form the PAC in netrin 1a or dcc morphants is phenocopied by laser ablation of motoneurons and is rescued both by cellular transplants and overexpression of dcc mRNA. These results provide a definitive example of the requirement of axons in endothelial guidance leading to the parallel patterning of nerves and vessels in vivo.
神经和血管系统共享共同的导向线索，这些线索对神经和内皮细胞具有直接和独立的信号作用。在这里，我们表明斑马鱼 Netrin 1a 指导 Dcc 介导的运动神经元的轴突导向，并且这种神经导向功能对于淋巴管生成是必需的。具体而言，水平肌隔（HMS）中的肌肉先驱分泌的 Netrin 1a 对于表达 dcc 的颅侧初级运动神经元（RoP）轴突和 HMS 中相邻的轴突的出芽是必需的，这些轴突与未来的 parachordal 链（PAC）的轨迹相邻。这些轴突对于 PAC 的形成以及随后的胸导管的形成是必需的。在 netrin 1a 或 dcc 形态发生体中，PAC 无法形成，这与运动神经元的激光消融是一致的，并且通过细胞移植和 dcc mRNA 的过表达都可以挽救。这些结果提供了一个明确的例子，说明了轴突在血管内皮导向中的要求，导致体内神经和血管的平行模式形成。
