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Transcription factor Sox11 is essential for both embryonic and adult neurogenesis

机译:转录因子Sox11对于胚胎和成人神经发生均必不可少

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Background: Neurogenesis requires neural progenitor cell (NPC) proliferation, neuronal migration, and differentiation. During embryonic development, neurons are generated in specific areas of the developing neuroepithelium and migrate to their appropriate positions. In the adult brain, neurogenesis continues in the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ) of the lateral ventricle. Although neurogenesis is fundamental to brain development and function, our understanding of the molecular mechanisms that regulate neurogenesis is still limited. Results: In this study, we generated a Sox11 floxed allele and a Sox11 null allele in mice using the Cre-loxP technology. We first analyzed the role of the transcription factor Sox11 in embryonic neurogenesis using Sox11 null embryos. We also examined the role of Sox11 in adult hippocampal neurogenesis using Sox11 conditional knockout mice in which Sox11 is specifically deleted in adult NPCs. Sox11 null embryos developed small and disorganized brains, accompanied by transient proliferation deficits in NPCs. Deletion of Sox11 in adult NPCs blunted proliferation in the SGZ. Using functional genomics, we identified potential downstream target genes of Sox11. Conclusions: Taken together, our work provides evidence that Sox11 is required for both embryonic and adult neurogenesis, and identifies potential downstream target genes.
机译:背景:神经发生需要神经祖细胞(NPC)增殖,神经元迁移和分化。在胚胎发育过程中,神经元在发育中的神经上皮的特定区域生成,并迁移到其适当位置。在成年大脑中,神经发生在海马齿状回的颗粒下区域(SGZ)和侧脑室的脑室下区域(SVZ)继续进行。尽管神经发生是大脑发育和功能的基础,但我们对调节神经发生的分子机制的理解仍然有限。结果:在这项研究中,我们使用Cre-loxP技术在小鼠中产生了Sox11连锁等位基因和Sox11无效等位基因。我们首先使用Sox11空胚分析了转录因子Sox11在胚胎神经发生中的作用。我们还研究了Sox11在成年海马神经发生中的作用,其中使用了Sox11条件敲除小鼠,其中在成年NPC中特异性删除了Sox11。 Sox11无效胚胎发育出大脑小而混乱,并伴随NPC的短暂增殖缺陷。成年NPC中Sox11的缺失抑制了SGZ中的增殖。使用功能基因组学,我们确定了Sox11的潜在下游靶基因。结论:综上所述,我们的工作提供了证据,表明胚胎和成年神经发生均需要Sox11,并确定了潜在的下游靶基因。

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