Identifying the role of DNMT1 in gene expression regulation in somatostatinergic interneurons during embryonic corticogenesis [RNA-Seq]

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 basal telencephalon 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，是皮层发生阶段的一项精细调控事件，对功能性大脑的形成至关重要。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端脑基底部（basal telencephalon）迁移至大脑皮层。该迁移过程受到内在遗传程序与外源性信号的协同调控。本研究旨在明确DNA甲基转移酶1（DNMT1）在调控小鼠皮层中间神经元发育相关关键基因表达，以及发育中大脑皮层内生长抑素阳性中间神经元迁移过程中的作用。我们从多只E14.5胎鼠的脑组织中，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；这些胎鼠的生长抑素能中间神经元分别存在或不存在Dnmt1条件性敲除，并按基因型合并样本。在完成RNA提取与文库制备后，对样本进行了测序。