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Intricate neural circuits are formed during neural development mainly by chemotropism-dependentmechanisms. Families of molecules essential for neuronal wiring have beenidentified to influencethe pathfinding decisions of neuronal growth cones. We are interested in the molecular and cellularmechanisms underlying axon guidance and regene-ration. We have established an in vitro modelsystem to quantitatively analyze the s-teering decisions of a neuronal growth cone in a defined gradientof guidance cues u-sing cultured neurons. To compliment the in vitro analysis，we have alsodeveloped a-n in vivo model system to examine midline axon guidance of commissural interneuronsinthe spinal cord of developing Xenopus embryos. Our recent efforts have been focused on the role ofCa2+，an important second messenger in almost all cell types in resp-onse to environmentalstimuli. We have identified TRPC1 as a major mediator of Ca2+ influx in response to a selectivegroup of guidance cues. Using pharmacological and m-olecular approaches to manipulate TRPCsignaling，we obtained evidence that TRPC act-ivation is required for growth cone turning of culturedneurons to developmental gui-dance cues as well as factors that inhibit axonal regeneration inadult. We furthershowed that such signaling is required for midline axon guidance of commissuralintern-eurons in developing embryonic spinal cord in vivo. Our latest findings on TrpC sig-naling inneuronal pathfinding will be discussed.