Interneuron odyssey: molecular mechanisms of tangential migration

Frontiers in Neural Circuits

Neuroscience

Asmaa Toumi¹  Ikram Toudji²  Émile Chamberland²  Elsa Rossignol³ 

[1] Centre Hospitalier Universitaire (CHU) Sainte-Justine Research Center, Montréal, QC, Canada;Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC, Canada;Centre Hospitalier Universitaire (CHU) Sainte-Justine Research Center, Montréal, QC, Canada;Department of Neurosciences, Université de Montréal, Montréal, QC, Canada;Centre Hospitalier Universitaire (CHU) Sainte-Justine Research Center, Montréal, QC, Canada;Department of Neurosciences, Université de Montréal, Montréal, QC, Canada;Department of Pediatrics, Université de Montréal, Montréal, QC, Canada;

关键词: GABA;    interneurons;    migration;    blood vessels;    oligodendrocytes;    cytoskeleton;    neurodevelopmental disorders;    therapy;   

DOI  :  10.3389/fncir.2023.1256455

 received in 2023-07-10, accepted in 2023-08-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved in various brain functions, including signal processing, learning, memory and adaptative responses. Disruption of cortical GABAergic interneuron migration thus induces profound deficits in neural network organization and function, and results in a variety of neurodevelopmental and neuropsychiatric disorders including epilepsy, intellectual disability, autism spectrum disorders and schizophrenia. It is thus of paramount importance to elucidate the specific mechanisms that govern the migration of interneurons to clarify some of the underlying disease mechanisms. GABAergic interneurons destined to populate the cortex arise from multipotent ventral progenitor cells located in the ganglionic eminences and pre-optic area. Post-mitotic interneurons exit their place of origin in the ventral forebrain and migrate dorsally using defined migratory streams to reach the cortical plate, which they enter through radial migration before dispersing to settle in their final laminar allocation. While migrating, cortical interneurons constantly change their morphology through the dynamic remodeling of actomyosin and microtubule cytoskeleton as they detect and integrate extracellular guidance cues generated by neuronal and non-neuronal sources distributed along their migratory routes. These processes ensure proper distribution of GABAergic interneurons across cortical areas and lamina, supporting the development of adequate network connectivity and brain function. This short review summarizes current knowledge on the cellular and molecular mechanisms controlling cortical GABAergic interneuron migration, with a focus on tangential migration, and addresses potential avenues for cell-based interneuron progenitor transplants in the treatment of neurodevelopmental disorders and epilepsy.

【 授权许可】

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Copyright © 2023 Toudji, Toumi, Chamberland and Rossignol.