CAMP-DEPENDENT GROWTH CONE GUIDANCE BY NETRIN-1

Netrin-1 is known to function as a chemoattractant for several classes of developing axons and as a chemorepellent for other classes of axon s, apparently dependent on the receptor type expressed by responsive c ells. In culture, growth cones of embryonic Xenopus spinal neurons exh ibited chemoattractive turning toward the source of netrin-1 but showe d chemorepulsive responses in the presence of a competitive analog of cAMP or an inhibitor of protein kinase A. Both attractive and repulsiv e responses were abolished by depleting extracellular calcium and by a dding a blocking antibody against the netrin-1 receptor Deleted in Col orectal Cancer. Thus, nerve growth cones may respond to the same guida nce cue with opposite turning behavior, dependent on other coincident signals that set the level of cytosolic cAMP.