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Synaptic-like Vesicles Facilitate Pioneer Axon Invasion.

Ev L Nichols | Cody J Smith
Current biology : CB | 2019

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.

Pubmed ID: 31378609

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This is a list of tools and resources that we have found mentioned in this publication.


SlideBook (tool)

RRID:SCR_014423

Digital microscopy software for research microscopy. It comes standard with drivers to control numerous instruments in and around the microscope. When online, data is acquired in a native-3D format over time, color and specimen locations in customizable experiment protocols. Data can be analyzed by a wide variety of tools for image processing including mathematical operations, statistics functions, analysis scripting and import to/export from MATLAB. Additional modules are available for special applications ranging from deconvolution to photomanipulation to multiphoton.

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SV2 (antibody)

RRID:AB_2315387

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Anti-MMP-14, C-Terminal antibody produced in rabbit (antibody)

RRID:AB_10744760

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Anti-Synapsin 1/2 (antibody)

RRID:AB_2622240

This polyclonal targets Synapsin 1/2

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RAB8A monoclonal antibody (M02), clone 3G1 (antibody)

RRID:AB_519014

This monoclonal targets RAB8A monoclonal antibody (M02) clone 3G1

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ZEISS ZEN Microscopy Software (software resource)

RRID:SCR_013672

User interface software for Carl Zeiss light microscopy imaging systems. ZEN is the universal user interface you will see on every imaging system from ZEISS. After selecting fluorophore, ZEN applies the necessary settings to collect and organize data.

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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SlideBook (software resource)

RRID:SCR_014300

Digital microscopy software for research microscopy. It comes standard with drivers to control numerous instruments in and around the microscope. When online, data is acquired in a native-3D format over time, color and specimen locations in customizable experiment protocols. Data can be analyzed by a wide variety of tools for image processing including mathematical operations, statistics functions, analysis scripting and import to/export from MATLAB. Additional modules are available for special applications ranging from deconvolution to photomanipulation to multiphoton.

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Imaris (software resource)

RRID:SCR_007370

Imaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.

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