Identifying the role of DNMT1 in gene expression regulation in somatostatinergic interneurons during embryonic corticogenesis

The establishment of neuronal circuits, made up of excitatory neurons and inhibitory interneurons, is a fine-tuned process during corticogenesis and is pivotal for a functional brain. Developmental aberrations affecting these circuits are implicated in several neuropsychiatric disorders. While excitatory neurons originate in cortical proliferative zones, inhibitory interneurons migrate from the basal telencephalon into the cortex. This migration is regulated by intrinsic genetic programs and extrinsic cues. Here, we aimed to identify the role of the DNA methyltransferase 1 (DNMT1) in controlling the expression of key genes implicated in mouse cortical interneuron development and the migration of somatostatin-expressing interneurons within the developing cortex. FAC-sorted somatostatinergic interneurons from the cortex were collected from the brains of multiple E14.5 mice, with or without a conditional knockout of Dnmt1 in somatostatinergic interneurons, and pooled per genotype. The samples were sequenced following an RNA extraction and library preparation.由兴奋性神经元与抑制性中间神经元构成的神经环路建立过程，是皮层发生阶段的精细调控事件，对功能性大脑的形成具有关键意义。影响此类神经环路的发育异常与多种神经精神疾病密切相关。兴奋性神经元起源于皮层增殖区，而抑制性中间神经元则从基底端脑迁移至皮层，该迁移过程受内在遗传程序与外在信号的共同调控。本研究旨在明确DNA甲基转移酶1（DNA methyltransferase 1, DNMT1）在调控小鼠皮层中间神经元发育相关关键基因表达，以及发育皮层内生长抑素能中间神经元迁移过程中的作用。我们从多只胚胎第14.5天（E14.5）小鼠的大脑皮层中，收集了经荧光激活细胞分选（FAC）得到的生长抑素能中间神经元，这些小鼠的生长抑素能中间神经元分别存在或不存在Dnmt1的条件性敲除，并按基因型对样本进行混合。在完成RNA提取与文库构建后，对样本进行了测序。