The Functional Roles of HDAC1 and HDAC2 in Neurodevelopment of the Mouse Brain

In this study, we explored the roles of histone deacetylases HDAC1 and HDAC2 in the developmental dynamics of the mouse brain. We discovered that these epigenetic regulators, HDAC1/2, are crucial in mediating the transition from neural epithelial cells (NEs) to radial glial cells (RGCs). To probe the epigenomic influence of HDAC1/2 on cortical development, we utilized a suite of techniques including RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and H3K27ac Cleavage Under Targets and Tagmentation (CUT&Tag) in both wild-type (WT) and HDAC1/2-deficient brain samples. Our analysis identified a significant dysregulation of numerous transcription-related genes in the HDAC1 and HDAC2 mutant brains. These findings underscore the critical role of HDAC1/2 as epigenetic modulators in the NE-to-RGC transition.