PUBLICATION
Pioneer axons utilize a dcc signaling-mediated invasion brake to precisely complete their pathfinding odyssey
- Authors
- Kikel-Coury, N.L., Green, L.A., Nichols, E.L., Zellmer, A.M., Pai, S., Hedlund, S.A., Marsden, K., Smith, C.J.
- ID
- ZDB-PUB-210705-2
- Date
- 2021
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 41(31): 6617-6636 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Axon Guidance/physiology*
- DCC Receptor/metabolism*
- Ganglia, Spinal/embryology
- Signal Transduction/physiology*
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 34131031 Full text @ J. Neurosci.
Citation
Kikel-Coury, N.L., Green, L.A., Nichols, E.L., Zellmer, A.M., Pai, S., Hedlund, S.A., Marsden, K., Smith, C.J. (2021) Pioneer axons utilize a dcc signaling-mediated invasion brake to precisely complete their pathfinding odyssey. The Journal of neuroscience : the official journal of the Society for Neuroscience. 41(31):6617-6636.
Abstract
Axons navigate through the embryo to construct a functional nervous system. A missing part of the axon navigation puzzle is how a single axon traverses distinct anatomical choice-points through its navigation. The dorsal root ganglia neurons experience such choice-points; first they navigate to the dorsal root entry zone, then halt navigation in the peripheral nervous system to invade the spinal cord, and then reinitiate navigation inside the CNS. Here, we used time-lapse super-resolution imaging in zebrafish DRG pioneer neurons to investigate how embryonic axons control their cytoskeleton to navigate to and invade at the correct anatomical position. We found that invadopodia components form in the growth cone even during filopodia-based navigation, but only stabilize when the axon is at the spinal cord entry location. Further, we show that intermediate levels of DCC and cAMP, as well as Rac1 activation, subsequently engage an axon invasion brake. Our results indicate that actin-based invadopodia components form in the growth cone and disruption of the invasion brake causes axon entry defects and results in failed behavioral responses, thereby demonstrating the importance of regulating distinct actin populations during navigational challenges.SIGNIFICANCE STATEMENT:Correct spatiotemporal navigation of neuronal growth cones is dependent upon extracellular navigational cues and growth cone dynamics. Here, we link dcc-mediated signaling to actin-based invadopodia and filopodia dynamics during pathfinding and entry into the spinal cord using an in vivo model of dorsal root ganglia sensory axons. We reveal a molecularly-controlled brake on invadopodia stabilization until the sensory neuron growth cone is present at the dorsal root entry zone, which is ultimately essential for growth cone entry into the spinal cord and behavioral response.
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Human Disease / Model
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