title: Impaired Interneuron Development after Foxg1 Disruption.
abstract: Interneurons play pivotal roles in the modulation of cortical function; however, the mechanisms that control interneuron development remain unclear. This study aimed to explore a new role for Foxg1 in interneuron development. By crossing Foxg1fl/fl mice with a Dlx5/6-Cre line, we determined that conditional disruption of Foxg1 in the subpallium results in defects in interneuron development. In developing interneurons, the expression levels of several receptors, including roundabout-1, Eph receptor A4, and C-X-C motif receptor 4/7, were strongly downregulated, which led to migration defects after Foxg1 ablation. The transcription factors Dlx1/2 and Mash1, which have been reported to be involved in interneuron development, were significantly upregulated at the mRNA levels. Foxg1 mutant cells developed shorter neurites and fewer branches and displayed severe migration defects in vitro. Notably, Prox1, which is a transcription factor that functions as a key regulator in the development of excitatory neurons, was also dramatically upregulated at both the mRNA and protein levels, suggesting that Prox1 is also important for interneuron development. Our work demonstrates that Foxg1 may act as a critical upstream regulator of Dlx1/2, Mash1, and Prox1 to control interneuron development. These findings will further our understanding of the molecular mechanisms of interneuron development.
authors.affiliation: Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Anatomy and Neuroscience, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Anatomy and Neuroscience, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Anatomy and Neuroscience, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Anatomy and Neuroscience, School of Medicine, Southeast University, Nanjing 210009, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Su
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Zhengang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Anatomy and Neuroscience, School of Medicine, Southeast University, Nanjing 210009, China.|Center of Depression, Beijing Institute for Brain Disorders, Beijing 100069, China.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D000071446:Neuronal Outgrowth / Q000502:physiology; D012333:RNA, Messenger; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C499317:Ascl1 protein, mouse; C088334:Distal-less homeobox proteins; C501120:Dlx5 protein, mouse; C100597:Dlx6 protein, mouse; C489565:Foxg1 protein, mouse
keywords: Dlx1/2; Foxg1; Mash1; Prox1; interneuron