Figure 1. Overview of signaling and mechanical events during bidirectional growth cone guidance.

(a) Involvement of second messengers in signal transduction. A guidance cue gradient causes asymmetric occupancy of guidance cue receptors across the growth cone (Step 1) and initial generation of second messengers such as Ca²⁺ (orange) and cyclic nucleotides (Step 2). Second messenger networks determine whether the growth cone turns toward or away from the side with Ca²⁺ signals (Step 3) and may amplify guidance information into steeply graded or even compartmentalized signals in the growth cone (Step 4). Steps 3 and 4 may be functionally coupled and temporally overlapping processes. (b) Steering machinery for growth cone guidance. Amplified signals on one side of the growth cone break the symmetry of membrane trafficking, cytoskeletal organization and adhesiveness, which causes attractive or repulsive turning of the growth cone (Step 5). Listed in the box are examples of regulators of the cytoskeleton and adhesion dynamics that are either activated or inactivated by Ca²⁺, cyclic nucleotides, and other signaling components.