Dissecting the cell autonomous and non-autonomous effects of DNMT1 deletion in cortical somatostatinergic interneurons

The development of cortical circuits, made up of excitatory neurons and inhibitory interneurons, is a fine-tuned and vital process during brain development. Aberrations affecting the establishment of these circuits are implicated in several neuropsychiatric and neurological 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 the development and migration of post-mitotic somatostatin-positive interneurons as well as its impact on the rest of the cortical population. Medial cortical tissue was dissected from brains of E16.5 mice with or without a conditional knockout of Dnmt1 in somatostatinergic interneurons. The nuclei were extracted via sucrose gradient ultracentrifugation and fixed. Following library preparation based on a split-and-pool approach, the samples were sequenced.