Kim JaeYeon, Poddar Aunoy, Sandoval Kadellyn, Chu Julia, Horton Emma, Cui Di, Nakamura Keira, Lu I-Ling, Mui Michael, Bartels Theresa, Wood Christian M, Ramos Susana I, Rowitch David H, Tsankova Nadejda M, Kim Hosung, Sherwood Chet C, Kramer Boris W, Roberts Angela C, Ross Pablo J, Xu Duan, Robertson Nicola J, Maga Elizabeth A, Ji Peng, Paredes Mercedes F
Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Nat Neurosci. 2025 Jul 14. doi: 10.1038/s41593-025-01987-2.
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 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.
在发育中的腹侧脑区产生的皮质GABA能中间神经元会远距离迁移至其最终目的地。虽然在新生儿人脑中存在中间神经元迁移的实例，但跨物种的产后迁移程度及其对皮质中间神经元组成的贡献仍不清楚。在这里，我们证明，包括人类、非人灵长类动物和仔猪在内的新生儿脑回脑具有一个精细的脑室下区，因其弯曲的形态和扩大的神经母细胞群体而被称为Arc。在无脑回的狨猴和小鼠脑中不存在Arc。转录组学和组织学方法显示，Arc神经元是来自内侧和尾侧神经节隆起的多种中间神经元，它们迁移到额叶、扣带回和颞叶皮质。与其他区域相比，Arc-皮质靶点的VIP神经元密度增加。我们的研究结果表明，Arc是一种发育结构，它支持产后神经元迁移的扩展，以实现脑回脑皮质中间神经元的模式形成。
