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The Journal of Neuroscience, October 1, 1998, 18(19):7930-7940
Interstitial Branches Develop from Active Regions of the Axon
Demarcated by the Primary Growth Cone during Pausing Behaviors
Györgyi
Szebenyi1,
John L.
Callaway1,
Erik W.
Dent2, and
Katherine
Kalil1, 2
1 Department of Anatomy and 2 Neuroscience
Training Program, University of Wisconsin, Madison, Wisconsin 53706
Interstitial branches arise from the axon shaft, sometimes at great
distances behind the primary growth cone. After a waiting period that
can last for days after extension of the primary growth cone past the
target, branches elongate toward their targets. Delayed interstitial
branching is an important but little understood mechanism for target
innervation in the developing CNS of vertebrates. One possible
mechanism of collateral branch formation is that the axon shaft
responds to target-derived signals independent of the primary growth
cone. Another possibility is that the primary growth cone recognizes
the target and demarcates specific regions of the axon for future
branching. To address whether behaviors of the primary growth cone and
development of interstitial branches are related, we performed
high-resolution time-lapse imaging on dissociated sensorimotor cortical
neurons that branch interstitially in vivo. Imaging of
entire cortical neurons for periods of days revealed that the primary
growth cone pauses in regions in which axon branches later develop.
Pausing behaviors involve repeated cycles of collapse, retraction, and
extension during which growth cones enlarge and reorganize. Remnants of
reorganized growth cones are left behind on the axon shaft as active
filopodial or lamellar protrusions, and axon branches subsequently
emerge from these active regions of the axon shaft. In this study we
propose a new model to account for target innervation in
vivo by interstitial branching. Our model suggests that delayed
interstitial branching results directly from target recognition by the
primary growth cone.
Key words:
interstitial axonal branch; growth cone behavior; time-lapse imaging; cortical neuronal culture; target innervation; cortical development
Copyright © 1998 Society for Neuroscience 0270-6474/98/18197930-11$05.00/0
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