The growth cone can be thought of as the 'hand and eye' of a developing axon - one that possesses both sensory and motor functions. As a bridge between these two, the second messenger, calcium ion (Ca²⁺), is released upon guidance cue-receptor engagement, and instructs the growth cone turning machinery on the direction of turning.

The inositol 1,4,5-trisphosphate (IP₃) receptor (IP₃R) is one of the two major classes of Ca²⁺ channels that release Ca²⁺ from internal storage. Our lab has previously shown that after nerve growth factor (NGF) bound to and activated cell surface receptors, the resultant generation of IP₃ formed a gradient across the growth cone (high on the side facing the NGF source, i.e. the 'near side'). IP₃ activated IP₃R, and in turn created a gradient of Ca²⁺ elevation inside the growth cone. Such asymmetric Ca²⁺ signal enabled attractive growth cone turning.

In vertebrates, there are three separate genes coding for three IP₃R subtypes. My data show that IP₃R type 3 (IP₃R3) is necessary for the NGF turning response. In vitro , growth cones from IP₃R3 knockout mice migrate straight forwards rather than turning towards the source of NGF, as in wildtype growth cones. Surprisingly, these IP₃R3 knockout growth cones are still able to generate Ca²⁺ elevations in response to NGF. However, the Ca²⁺ signal spreads to the far side, in contrast to the wildtype counterpart in which Ca²⁺ elevation is localized to the near side only. These data indicate that IP₃R3 is needed for the asymmetry in the Ca²⁺ response, and thus for growth cone turning.