WNT signalling control by KDM5C during development affects cognition.

ABSTRACT: Although KDM5C is one of the most frequently mutated genes in X-linked intellectual disability¹, the exact mechanisms that lead to cognitive impairment remain unknown. Here we use human patient-derived induced pluripotent stem cells and Kdm5c knockout mice to conduct cellular, transcriptomic, chromatin and behavioural studies. KDM5C is identified as a safeguard to ensure that neurodevelopment occurs at an appropriate timescale, the disruption of which leads to intellectual disability. Specifically, there is a developmental window during which KDM5C directly controls WNT output to regulate the timely transition of primary to intermediate progenitor cells and consequently neurogenesis. Treatment with WNT signalling modulators at specific times reveal that only a transient alterati

SUBMITTER: Karwacki-Neisius V 

PROVIDER: S-EPMC10954547 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature