Roles of Arx in developing interneuron [ChIP-seq]

Abnormal cortical interneuron (cIN) development and function has been linked to neurodevelopmental disorders including developmental epilepsies, intellectual disabilities, and autism spectrum disorder. Mutations in ARX (aristaless-related homeobox) are associated with these disorders. Its differential expression in projection neuron- versus interneuron progenitors suggests ARX is one of the few genes with distinct functions in each progenitor type. To investigate how ARX regulates development of cINs, which originate from the ganglionic eminence (GE) and migrate to the cortex, we interrogated multiple GE-targeted Arx mutant mice. Our data demonstrates that ARX normally represses Nkx2.1 expression and promotes cell cycle exit of the progenitor cells. Furthermore, it plays key roles in cIN subtype specification and migration along the marginal zone, by directly binding to the regulatory sequences of genes modulating cell subtype specification and cell-cell communication. Together these findings provide new insights into the mechanisms underlying cIN development and migration and how they are disrupted in several related disorders. Overall design: To identify Arx interaction regions in mouse genome, Arx protein complex were precipitated with E14.5 telencephalon using anti-Arx antibody (ChIP-seq).