The precision with which neurons form connections is crucial for the normal development and function of the nervous system. The development of neuronal circuitry in the nervous system is accomplished by axon pathfinding: a process where growth cones guide axons through the embryonic environment to connect with their appropriate synaptic partners to form functional circuits. Despite intense efforts over many years to understand how this process is regulated, the complete repertoire of molecular mechanisms that govern the growth cone cytoskeleton and hence motility, remain unresolved. A central tenet in the axon guidance field is that calcium signals regulate growth cone behaviours such as extension, turning and pausing by regulating rearrangements of the growth cone cytoskeleton. Here, we provide evidence that not only the amplitude of a calcium signal is critical for growth cone motility but also the source of calcium mobilisation. We provide an example of this idea by demonstrating that manipulation of calcium signalling via L-type voltage gated calcium channels can perturb sensory neuron motility towards a source of netrin-1. Understanding how calcium signals can be transduced to initiate cytoskeletal changes represents a significant gap in our current knowledge of the mechanisms that govern axon guidance, and consequently the formation of functional neural circuits in the developing nervous system.

神经元形成连接的精确度对于神经系统的正常发育和功能至关重要。神经系统中神经元回路的发展是通过轴突寻路来完成的：轴突通过胚胎发育环境引导轴突与适当的突触伙伴连接以形成功能回路。尽管多年来人们为了解如何调节这一过程付出了巨大的努力，但仍未解决控制生长锥细胞骨架并因此决定其运动性的分子机制的全部内容。轴突指导领域的中心宗旨是钙信号通过调节生长锥细胞骨架的重排来调节生长锥行为，例如延伸，转向和暂停。这里，我们提供的证据表明，不仅钙信号的幅度对于生长锥的运动至关重要，而且对钙动员的来源也至关重要。我们通过证明通过L型电压门控钙通道对钙信号的操纵可以扰动感觉神经元向netrin-1来源的运动，提供了这个想法的一个例子。了解钙离子如何被转导以引发细胞骨架变化，这代表了我们目前对控制轴突引导机制的知识的巨大空白，因此在发育中的神经系统中形成了功能性神经回路。我们通过证明通过L型电压门控钙通道对钙信号的操纵可以扰动感觉神经元向netrin-1来源的运动，提供了这个想法的一个例子。了解钙离子如何被转导以引发细胞骨架变化，这代表了我们目前对控制轴突引导机制的知识的巨大空白，因此在发育中的神经系统中形成了功能性神经回路。我们通过证明通过L型电压门控钙通道对钙信号的操纵可以扰动感觉神经元向netrin-1来源的运动，提供了这个想法的一个例子。了解钙离子如何被转导以引发细胞骨架变化，这代表了我们目前对控制轴突引导机制的知识的巨大空白，因此在发育中的神经系统中形成了功能性神经回路。