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Foxg1 regulates the postnatal radial migration of cortical Interneurons

Foxg1 regulates the postnatal radial migration of cortical I...

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中国神经科学学会第十二届全国学术会议

作者： Wei Shen Ru Ba Yan Su Yang Ni Dong Sheng Li-Juan Zhu Chunjie Zhao Key Laboratory of Developmental Genes and Human Diseases MOELife Science InstituteSoutheast University Department of Anatomy and Neuroscience School of Medicine Southeast University

Abnormalities in cortical interneurons are usually closely associated with neurological disorders such as epilepsy（Meyer et al., 2011）. Most patients with Foxg1 syndrome experience seizures, suggesting that Foxg1 has important roles in the development of cortical interneurons. According to our previous study, Foxg1 has significant functions in the tangential migration of cortical interneurons during embryonic development. Here, we explored its role in radial migration by deleting Foxg1 during postnatal development, which was achieved by crossing Foxg1 fl/fl mice with the Gad2-Cre ER line and treating the mice with tamoxifen. Ablation of Foxg1 resulted in impaired distributions of somatostatin-, calretinin-, and neuropeptide Y-positive interneurons in the cortex. Further investigations revealed that the migration capacity of cortical interneurons was significantly decreased, accompanied by a downregulation of C-X-C chemokine receptor 4（CXCR4） expression. Distal-less homeobox 1（Dlx1） expression was also decreased, resulting in the upregulation of Pak3 expression and ultimately the enhanced dendritic complexity of mutant interneurons, which may also be responsible for their decreased migration capacity. We further found that Foxg1 does not function upstream of KCC2 to regulate the termination of radial migration of cortical interneurons. Due to the imbalanced neural circuit, Foxg1 mutant mice showed increased seizure susceptibility in a pentylenetetrazole induction assay. Our work demonstrated that Foxg1 regulated the radial migration of cortical interneurons by preserving their migration capacity. These findings will improve our understanding of the radial migration of interneurons and help to elucidate the mechanisms underlying seizure symptoms in patients with Foxg1 syndrome.

关键词： interneurons radial migration Foxg1 CXCR4 Dlx1 zeizure

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