An expanded subventricular zone supports postnatal cortical interneuron migration in gyrencephalic brains
Cortical GABAergic interneurons generated in the ventral developing brain travel long distances to their final destinations. While there are examples of interneuron migration in the neonatal human brain, the extent of postnatal migration across species and how it contributes to cortical interneuron composition remains unknown. Here we demonstrate that neonatal gyrencephalic brains, including humans, nonhuman primates and piglets, harbor an elaborate subventricular zone, termed the Arc, due to its curved morphology and expanded neuroblast populations. The Arc is absent in lissencephalic marmoset and mouse brains. Transcriptomic and histological approaches revealed that Arc neurons are diverse interneurons from the medial and caudal ganglionic eminences that migrate into the frontal, cingulate and temporal cortex. Arc-cortical targets exhibit an increase in VIP<sup>+</sup> neuronal density compared to other regions. Our findings reveal that the Arc is a developmental structure that supports the expansion of postnatal neuronal migration for cortical interneuron patterning in gyrencephalic brains.
Authors
- Elizabeth A. Maga (ORCID: https://orcid.org/0000-0002-3784-6961)
- Peng Ji (ORCID: https://orcid.org/0000-0002-7447-5688)
- Susana Isabel Ramos (ORCID: https://orcid.org/0000-0003-2886-6781)
- Theresa Bartels (ORCID: https://orcid.org/0000-0003-4100-0608)
- Mercedes F. Paredes (ORCID: https://orcid.org/0000-0003-2503-1447)
- Hosung Kim (ORCID: https://orcid.org/0000-0002-2269-8644)
- Di Cui (ORCID: https://orcid.org/0000-0003-1086-2192)
- I-Ling Lu (ORCID: https://orcid.org/0000-0003-2311-1304)
- Duan Xu (ORCID: https://orcid.org/0000-0003-0550-4235)
- Emma C. Horton (ORCID: https://orcid.org/0000-0001-9730-7380)
- Nicola Jayne Robertson (ORCID: https://orcid.org/0000-0002-5783-0828)
- David H. Rowitch (ORCID: https://orcid.org/0000-0002-0079-0060)
- Chet C. Sherwood (ORCID: https://orcid.org/0000-0001-6711-449X)
- Christian M. Wood (ORCID: https://orcid.org/0000-0003-1267-5032)
- Michael H. Mui (ORCID: https://orcid.org/0000-0003-1985-376X)
- Angela Roberts (ORCID: https://orcid.org/0000-0003-2873-157X)
- Kadellyn Sandoval (ORCID: https://orcid.org/0000-0001-5923-8337)
- Aunoy Poddar (ORCID: https://orcid.org/0000-0002-5065-7321)
- Pablo J. Ross (ORCID: https://orcid.org/0000-0002-3972-3754)
- Jae Yeon Kim (ORCID: https://orcid.org/0000-0002-0542-9071)
- Keira Nakamura (ORCID: https://orcid.org/0009-0009-8054-6049)
- Julia Chu (ORCID: https://orcid.org/0000-0003-4956-2189)
- Boris W. Kramer
- Nadejda M. Tsankova (ORCID: https://orcid.org/0009-0007-0943-3872)
Institutions
- University of Southern California (US)
- Poznan University of Medical Sciences (PL)
- University of California, Merced (US)
- University of California, San Francisco (US)
- George Washington University (US)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- University of California San Francisco Medical Center (US)
- London Women's Clinic (GB)
- Broad Center (US)
- University College London (GB)
- University of California, Davis (US)
- University of Edinburgh (GB)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Nature Neuroscience
- Published
- 2025-07-14
- DOI
- https://doi.org/10.1038/s41593-025-01987-2
- Citations
- 7
- Primary Topic
- Neurogenesis and neuroplasticity mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 9.23
Funders
- National Institute of Neurological Disorders and Stroke