Violetta Karwacki-Neisius, Ahram Jang, Engin Cukuroglu, Albert Tai, Alan Jiao, Danilo Predes, Joon Yoon, Emily Brookes, Jiekai Chen, Aimee Iberg, Florian Halbritter, Katrin Õunap, Jozef Gecz, Thorsten M Schlaeger, Shannan Ho Sui, Jonathan Göke, Xi He, Maria K Lehtinen, Scott L Pomeroy, Yang Shi
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...
February 21, 2024: Nature