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Serial Synapse Formation through Filopodial Competition for Synaptic Seeding Factors
M Neset Özel1, Abhishek Kulkarni2, Amr Hasan2
1Division of Neurobiology, Institute for Biology, Freie Universität Berlin, 14195 Berlin, Germany; Neuroscience Graduate Program, UT Southwestern Medical Center Dallas, Dallas, TX 75390, USA.
Developmental Cell
|July 30, 2019
Summary
Developing brains form synapses through a "serial synapse formation" model. A few filopodia suppress others, ensuring appropriate synapse numbers and robust brain connectivity.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Axon pathfinding involves growth cones exploring with filopodia before synapse formation.
- Ensuring robust brain connectivity requires understanding the interplay between filopodial dynamics and synapse assembly.
Purpose of the Study:
- To investigate the mechanisms governing synapse formation in developing Drosophila R7 photoreceptor axons.
- To elucidate the role of filopodial dynamics and synaptic seeding factors in regulating synapse number.
Main Methods:
- Developed a novel 4D analysis method to track filopodial dynamics in real-time.
- Created a data-driven computational model to simulate synapse formation processes.
- Utilized live imaging in developing Drosophila brains.
Main Results:
- Supported a "serial synapse formation" model where 1-2 filopodia are actively synaptogenic at any time.
- Identified competition for synaptic seeding factors as a mechanism for suppressing other filopodia.
- Demonstrated that loss of Syd-1 and Liprin-α disrupts suppression, leading to filopodial destabilization and reduced synapse formation.
- Observed that synapse formation failure can cause axon terminal retraction.
Conclusions:
- A filopodial "winner-takes-all" mechanism ensures the correct number of synapses are formed.
- Synaptic seeding factors play a critical role in stabilizing specific filopodia for synapse development.
- This study provides insights into the precise regulation of neural connectivity during development.
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