TY - JOUR
T1 - Cyclic nucleotide-dependent switching of mammalian axon guidance depends on gradient steepness
AU - Thompson, Andrew W.
AU - Pujic, Zac
AU - Richards, Linda J.
AU - Goodhill, Geoffrey J.
N1 - Funding Information:
We thank Timothy Vaughan for developing the software for analysis of neurite trajectories. Funding comes from the Australian Research Council (Discovery Grant DP0666126 ), and the Australian National Health and Medical Research Council (Project Grants 456003 , 631532 , Principal Research Fellowship to LJR).
PY - 2011/5
Y1 - 2011/5
N2 - Correct wiring of the nervous system during development requires axons to respond appropriately to gradients of attractive and repulsive guidance cues. However, the steepness and concentration of these gradients vary in vivo, for instance, with distance from the target. Understanding how these changing conditions affect the navigation strategies used by developing axons is important for understanding how they are guided over long distances. Previous work has shown that cyclic nucleotide levels determine whether axons are attracted or repelled by steep gradients of the same guidance cue, but it is unknown whether this is also true for shallow gradients. We therefore investigated the guidance responses of rat superior cervical ganglion (SCG) axons in both steep and shallow gradients of nerve growth factor (NGF). In steep gradients we found that cyclic nucleotide-dependent switching occurred, consistent with previous reports. Surprisingly however, we found that in shallow NGF gradients, cyclic nucleotide-dependent switching did not occur. These results suggest that there may be substantial differences in the way axons respond to gradient-based guidance cues depending on where they are within the gradient.
AB - Correct wiring of the nervous system during development requires axons to respond appropriately to gradients of attractive and repulsive guidance cues. However, the steepness and concentration of these gradients vary in vivo, for instance, with distance from the target. Understanding how these changing conditions affect the navigation strategies used by developing axons is important for understanding how they are guided over long distances. Previous work has shown that cyclic nucleotide levels determine whether axons are attracted or repelled by steep gradients of the same guidance cue, but it is unknown whether this is also true for shallow gradients. We therefore investigated the guidance responses of rat superior cervical ganglion (SCG) axons in both steep and shallow gradients of nerve growth factor (NGF). In steep gradients we found that cyclic nucleotide-dependent switching occurred, consistent with previous reports. Surprisingly however, we found that in shallow NGF gradients, cyclic nucleotide-dependent switching did not occur. These results suggest that there may be substantial differences in the way axons respond to gradient-based guidance cues depending on where they are within the gradient.
KW - Axon guidance
KW - Cyclic AMP (cAMP)
KW - Growth cone
KW - Navigation
KW - Nerve growth factor (NGF)
KW - Regeneration
UR - http://www.scopus.com/inward/record.url?scp=79955479009&partnerID=8YFLogxK
U2 - 10.1016/j.mcn.2011.02.012
DO - 10.1016/j.mcn.2011.02.012
M3 - Article
C2 - 21376124
AN - SCOPUS:79955479009
SN - 1044-7431
VL - 47
SP - 45
EP - 52
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 1
ER -