PUBLICATION

Synaptic-like Vesicles Facilitate Pioneer Axon Invasion

Authors
Nichols, E.L., Smith, C.J.
ID
ZDB-PUB-190807-1
Date
2019
Source
Current biology : CB   29(16): 2652-2664.e4 (Journal)
Registered Authors
Keywords
DREZ, axon guidance, development, dorsal root ganglia, invasion, matrix metalloproteinase, synaptic vesicles, zebrafish
MeSH Terms
  • Animals
  • Axons/physiology*
  • Ganglia, Spinal/physiology*
  • Growth Cones/physiology*
  • Synaptic Vesicles/physiology*
  • Zebrafish/physiology*
PubMed
31378609 Full text @ Curr. Biol.
Abstract
Synaptic vesicles are indispensable for neuronal communication in mature circuits. Synaptic vesicle biogenesis must be concurrent with axon navigation for synaptogenesis, but whether synaptic vesicles are functionally employed in circuit formation before synaptogenesis is poorly understood. Here, we use time-lapse imaging and transgenesis in zebrafish to visualize the role of synaptic-like vesicles in navigation of dorsal root ganglia pioneer axons. We identify that synaptic-like vesicles accumulate in the central growth cone as the pioneer axon breaches the spinal boundary at the dorsal root entry zone. Inhibition of vesicle release with cell-specific tetanus toxin expression results in pioneer axon pathfinding defects and altered spinal entry. We further show that the matrix metalloproteinase (MMP) mmp14a is required in pioneer axons to navigate across the boundary of the spinal cord and, with super-resolution microscopy, is positioned with synaptic vesicles at the boundary. Manipulations of concurrent actin reorganization reveal that actin remodeling drives vesicle release and subsequent MMP activity. Together, these data point to an indispensable role for synaptic-like vesicles at specific points in axon navigation as regulators of growth cone microenvironment.
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