Evolution Shapes Cortical Interneuron Migration
The cerebral cortex comprises excitatory neurons and inhibitory interneurons originating from distinct forebrain regions. During migration, cortical interneurons (cINs) interact dynamically with neighbouring cells and their microenvironment, contributing to cortical architecture. However, how evolutionary changes in cIN migration shape species-specific cortical development remains unclear. Comparative analyses in mouse, ferret, and human models revealed a conserved migratory sequence but distinct behaviours: human cINs migrate slower, display increased leading-process branching, and exhibit more frequent homotypic repulsive interactions than their mouse and ferret counterparts. These features promote dispersed cortical invasion of cINs in humans and ferrets, contrasting with the stream-like migration observed in mice. Mechanistically, elevated expression of the cytosolic carboxypeptidase CCP1 in human cINs reduces microtubule glutamylation and doublecortin recruitment, thereby facilitating leading-process branching. These findings identify a CCP1-dependent mechanism regulating cIN dispersion and suggest that evolutionary changes in cIN migration contribute to divergent patterns of cortical morphogenesis across mammals.
Authors
- Christopher Kune (ORCID: https://orcid.org/0000-0002-3010-8173)
- Ekaterina A. Epifanova (ORCID: https://orcid.org/0000-0003-4640-7917)
- Antonela Bonafina (ORCID: https://orcid.org/0000-0002-6694-8449)
- Ryohei Iwata (ORCID: https://orcid.org/0000-0001-7371-3157)
- Romain Le Bail (ORCID: https://orcid.org/0000-0002-2690-4214)
- Gabriel Mazzucchelli (ORCID: https://orcid.org/0000-0002-8757-8133)
- Anne Firquet
- Bernard Lakaye (ORCID: https://orcid.org/0000-0002-3850-2175)
- Romann Close
- Pierre Vanderhaeghen (ORCID: https://orcid.org/0000-0001-7899-5720)
- Vı́ctor Borrell (ORCID: https://orcid.org/0000-0002-7833-3978)
- Silvia Cappello (ORCID: https://orcid.org/0000-0003-1553-6775)
- Laurent Nguyen (ORCID: https://orcid.org/0000-0002-8560-3008)
- Adrián Cárdenas (ORCID: https://orcid.org/0000-0001-5532-4481)
- Sylvia Tielens
- Bernard Coumans
- Carsten Janke (ORCID: https://orcid.org/0000-0001-7053-2000)
- Hannah Bruce
- Anaïs Boutsen
- Haw-Yuan Cheng
- Natali Rasetto
- Isabel Gallego-Lopez
- Sophie Perrier d'Hauterive
- Miriam Javier-Torrent
- Jean-Yves Raty
Institutions
- Consejo Superior de Investigaciones Científicas (ES)
- University of Liège (BE)
- VIB-KU Leuven Center for Microbiology (BE)
- Centre hospitalier régional de la Citadelle (BE)
- Institut Curie (FR)
- Ludwig-Maximilians-Universität München (DE)
- KU Leuven (BE)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-11-03
- DOI
- https://doi.org/10.64898/2026.11.02.763736
- Primary Topic
- Neurogenesis and neuroplasticity mechanisms
- Type
- preprint