We have tested whether the orientation of axons sprouting from bipolar
dorsal root ganglion neurons is influenced by diffusible cues from su
rrounding tissues. Surface ectoderm, dermomyotome, and notochord exert
strong chemorepulsion on axons growing in collagen gels, operating at
separations beyond those found in vivo and active in cocultures of ch
ick and mouse tissues. Basal and alar plates of the neural tube are de
void of activity, as is the posterior-half-sclerotome, which repels in
a contact-dependent manner. When ganglia are sandwiched between dermo
myotome and notochord placed at a distance, axon growth is channeled i
n a bipolar trajectory. These results show that gradients of diffusibl
e repulsion molecules flanking axon pathways can generate linear patte
rns of axon growth. We suggest that such ''surround repulsion'' may fu
nction generally, in concert with contact-dependent guidance mechanism
s, to guide axons in the developing nervous system.