Fig 7. Shh and Netrin-1 synergize to guide commissural axons when their gradients are shallow.

(A) In shallow individual cue gradients, commissural axon turning is random (left and middle). In the presence of combined Shh and Netrin-1 shallow gradients (right), axons turn toward the higher concentration of guidance cue. When either gradient alone is insufficient to promote axon turning, pSFK activation is also not polarized up the gradient. However, the combined Shh and Netrin-1 gradient biases pSFK distribution to the side of the growth cone facing up the gradient. (B) In the developing spinal cord, the gradients of Shh and Netrin-1 proximal to the floor plate are steep (high fractional change), whereas further from the floor plate, the gradients of Shh and Netrin-1 are shallow (low fractional change). (C) When either the Shh or Netrin-1 signaling pathway is disabled, guidance errors occur at approximately the midpoint of the spinal cord, where the gradients are shallow. Our results suggest that in this shallow gradient region, integrating multiple guidance cues is necessary for correct growth cone guidance.