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In Vivo Direct Reprogramming of Resident Glial Cells into Interneurons by Intracerebral Injection of Viral Vectors
Published on: June 17, 2019
Optimization of interneuron function by direct coupling of cell migration and axonal targeting.
Lynette Lim1,2,3, Janelle M P Pakan4,5, Martijn M Selten1,2
1Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Different interneuron migration routes in the embryonic brain are linked to their axon development. Disrupting Martinotti cell migration impairs their axonal targeting and function, revealing coupled developmental programs.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Neural circuit assembly requires coordinated cell migration and axon targeting.
- Cell-autonomous mechanisms coordinating these developmental events are poorly understood.
- Interneurons are crucial for cortical inhibitory circuit function.
Purpose of the Study:
- To investigate the relationship between interneuron migration routes and axon targeting.
- To elucidate the cell-autonomous mechanisms coordinating these processes.
- To understand how migration influences the assembly of cortical inhibitory circuits.
Main Methods:
- Utilized conditional gene deletion of Mafb in developing interneurons.
- Tracked interneuron migration routes within the embryonic cerebral cortex.
- Assessed axonal arborization and in vivo function of interneurons.
Main Results:
- Identified distinct migratory routes for different interneuron classes.
- Somatostatin-expressing interneurons migrating via the marginal zone develop into Martinotti cells with Layer 1 axonal arbors.
- Conditional deletion of Mafb cell-autonomously disrupted Martinotti cell migration, axonal development, and in vivo function.
Conclusions:
- Interneuron migration routes are coupled to specific axonal targeting programs.
- The Mafb gene plays a critical role in coordinating migration and axon development for Martinotti cells.
- These findings highlight the integration of developmental programs for optimal inhibitory circuit assembly.
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