Defining cis-regulatory elements and transcription factors that control human cortical interneuron development.

ABSTRACT: Although human cortical interneurons (cINs) are a minority population in the cerebral cortex, disruption of interneuron development is a frequent contributor to neurodevelopmental disorders. Here, we utilized a model for deriving cINs from human embryonic stem cells to profile chromatin state changes and generate an atlas of cis-regulatory elements (CREs) controlling human cIN development. We used these data to define candidate transcription factors (TFs) that may bind these CREs to regulate interneuron progenitor specification. Among these were RFX3 and RFX4, risk genes for autism spectrum disorder (ASD) with uncharacterized roles in human neuronal development. Using RFX3 and RFX4 knockdown models, we demonstrated new requirements for both genes in interneuron progenitor specificat

SUBMITTER: Chapman G 

PROVIDER: S-EPMC11140214 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature