文章基本信息

标题：Nf1 deletion results in depletion of the Lhx6 transcription factor and a specific loss of parvalbumin+ cortical interneurons
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作者：Kartik Angara ; Emily Ling-Lin Pai ; Stephanie M. Bilinovich 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：11
页码：6189-6195
DOI：10.1073/pnas.1915458117
出版社：The National Academy of Sciences of the United States of America
摘要：Neurofibromatosis 1 (NF1) is caused by mutations in the NF1 gene, which encodes the protein, neurofibromin, an inhibitor of Ras activity. Cortical GABAergic interneurons (CINs) are implicated in NF1 pathology, but the cellular and molecular changes to CINs are unknown. We deleted mouse Nf1 from the medial ganglionic eminence, which gives rise to both oligodendrocytes and CINs that express somatostatin and parvalbumin. Nf1 loss led to a persistence of immature oligodendrocytes that prevented later-generated oligodendrocytes from occupying the cortex. Moreover, molecular and cellular properties of parvalbumin (PV)-positive CINs were altered by the loss of Nf1 , without changes in somatostatin (SST)-positive CINs. We discovered that loss of Nf1 results in a dose-dependent decrease in Lhx6 expression, the transcription factor necessary to establish SST + and PV + CINs, which was rescued by the MEK inhibitor SL327, revealing a mechanism whereby a neurofibromin/Ras/MEK pathway regulates a critical CIN developmental milestone.
关键词：cortical interneuron ; oligodendrocyte ; MGE