大脑中投射神经元与其靶区之间特异精确连接是大脑功能神经环路的结构基础。目前人们对于大脑神经元投射路径选择分子机制的认识仍不充分。在本项目研究中，我们利用斑马鱼模式动物开展对神经元在端脑环路中投射路径选择分子机制研究。我们已有研究结果表明轴突导向因子DCC与Robo2在端脑神经元投射路径选择中起作用。本项目研究预实验结果表明轴突导向因子Unc5a以及Wnt信号通路可影响端脑神经元投射。我们将深入检测端脑神经元的分子特性并建立其投射路径选择的分子调控网络模型。我们将结合在整体动物发育过程中的分子功能分析，以期明确端脑神经元是如何整合信号分子的作用并如何通过调节其内在响应特性来完成对投射路径的选择。近来的研究结果表明在胚胎发育阶段参与神经环路形成过程的分子在神经损伤后再生及神经环路可塑性中起到重要的作用。鉴于此，我们的研究结果亦将有助于加深对脑损伤后再生的认识并有可能推动对脑损伤等疾病的治疗。

The precise connections between neurons and their targets form the structural basis of the functional neural circuits in the brain. The molecular mechanisms underlying neuronal pathfinding in the brain are not well understood. We take advantage of the zebrafish model to study how the telencephalic neurons make their axonal projection decisions within the forebrain neural circuits. Our previous work has shown that guidance receptor Dcc and Robo2 play important roles in such decisions. Our preliminary data showed that other guidance receptor such as Unc5a and signaling molecules such as Wnt may also play roles in the projection choices. We will further examine the molecular properties of the telencephalic neurons and determine the molecular network regulating the pathfinding choices. We will study the functional roles of the molecules involved in intact animals and investigate how the telencephalic neurons integrate the extrinsic signalings and regulate their intrinsic responses to coordinate the projection decisions. Recent studies have shown that molecules involved in the neural circuit formation during embryonic development may also participate in the circuit plasticity and regeneration. Thus, our results may provide insights for developing useful therapies to repair neural circuits after injury.