Developmental trajectories of GABAergic cortical interneurons are sequentially modulated by dynamic FoxG1 expression levels

• 成果类型: Article
• 署名作者: Miyoshi, Goichi; Ueta, Yoshifumi; Yagasaki, Yuki; Kishi, Yusuke; Fishell, Gord; Machold, Robert P.; Miyata, Mariko
• 署名单位: Gunma University; Tokyo Women's Medical University; New York University; University of Tokyo; University of Tokyo; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11633
• DOI: 10.1073/pnas.2317783121
• 发表日期: 2024-04-16
• 关键词: caudal ganglionic eminence; neuronal migration; tangential migration; circuit development; congenital variant; mental-retardation; cerebral-cortex; stem-cells; differentiation; diversity

摘要

GABAergic inhibitory interneurons, originating from the embryonic ventral forebrain territories, traverse a convoluted migratory path to reach the neocortex. These interneuron precursors undergo sequential phases of tangential and radial migration before settling into specific laminae during differentiation. Here, we show that the developmental trajectory of FoxG1 expression is dynamically controlled in these interneuron precursors at critical junctures of migration. By utilizing mouse genetic strategies, we elucidate the pivotal role of precise changes in FoxG1 expression levels during interneuron specification and migration. Our findings underscore the gene dosage-dependent function of FoxG1, aligning with clinical observations of FOXG1 haploinsufficiency and duplication in syndromic forms of autism spectrum disorders. In conclusion, our results reveal the finely tuned developmental clock governing cortical interneuron development, driven by temporal dynamics and the dose- dependent actions of FoxG1.