A Functional Role for REST Co-Repressor 2 (Rcor2) in Callosal Development

Pallial functional organization is mediated by the dynamic interplay of a broad spectrum of cellular and molecular cues that promote midline patterning, neurogenesis, axon guidance and neural connectivity. The regulators that orchestrate these seminal processes are still poorly understood. By employing a pallial conditional ablation model, we report that the transcriptional and epigenetic modulator, REST corepressor 2 (Rcor2) plays key roles in organizing the developing corticoseptal boundary. ChIP-seq and RNA-seq analyses reveal that Rcor2 modulates a diverse repertoire of classes of genes with essential roles in CC development, including pallial/subpallial patterning, cell fate specification and axon guidance. ChIP-sequencing performed on embryonic day 14.5 midline cortex of C57/Bl6 strain mice. Immunoprecipitation was carried out using an Rcor2 specific antibody, or a rabbit IgG non specific mock antibody. 2 replicates of each immunoprecipitation were multiplexed using the NEBnext II library prep kit and sequenced through Cornell epigenomcs core facility using a Hiseq2500 platform. RNA-seq was performed on E14.5 cortical midline comparing Rcor2f/f used as controls versus Rcor2f/f/EMX1-iCRE conditional knockouts. 2 Replicates per genotype were used. Multiplexed libraries were generated with the TRUseq Total RNA library prep kit, and sequenced on a Hiseq2500 platform by the Cornell epigenomics core facility.