Control of neuronal growth cone navigation by asymmetric inositol 1,4,5-trisphosphate signals

Inositol 1,4,5-trisphosphate (IP₃) is generally viewed as a global messenger that increases cytosolic calcium ion (Ca²⁺) concentration. However, the spatiotemporal dynamics of IP₃ and the functional significance of localized IP₃ production in cell polarity remain largely unknown. Here, we demonstrate the critical role of spatially restricted IP3 signals in axon guidance. We found that IP₃ and ensuing Ca²⁺ signals were produced asymmetrically across growth cones exposed to an extracellular gradient of nerve growth factor (NGF) and mediated growth cone turning responses to NGF. Moreover, photolysisinduced production of IP₃ on one side of a growth cone was sufficient to initiate growth cone turning toward the side with the higher concentration of IP₃. Thus, locally produced IP₃ encodes spatial information that polarizes the growth cone for guided migration.