PLX260971

GSE146595: Altered regional progenitor dynamics in the neocortexof a BBSOA disease mouse model

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

The relationships between impaired cortical development and consequent malformations in neurodevelopmental disorders, as well as the genes implicated in these processes, are not fully elucidated to date. In this study, we report six novel cases of patients affected by BBSOAS (Boonstra-Bosch-Schaff Optic AtrophySyndrome), a newly emerging rare neurodevelopmental disorder, caused by loss-of-function mutations of the transcriptional regulatorNR2F1.Young patients withNR2F1haploinsufficiency display mild to moderate intellectual disability and show reproducible polymicrogyria-like brain malformations in the parietal and occipital cortex. Using a recently established BBSOA mouse model, we found thatNr2f1regionally controls long-term self-renewal of neural progenitor cellsviamodulation of cell cycle genes and key cortical development master genes, such asPax6. In the human foetal cortex, distinct NR2F1 expression levels encompass gyri and sulci and correlate with local degrees of neurogenic activity. In addition, reduced NR2F1 levels in cerebral organoids affect neurogenesis andPAX6expression. We proposeNR2F1as an area-specific regulator of mouse and human brain morphology and a novel causative gene of abnormal gyrification. SOURCE: Seyed Mohammd Mahdi Rasa (Mahdi.Rasa@leibniz-fli.de) - Epigenetic (Francesco Neri) Leibniz Institute on Aging – Fritz Lipmann Institute (FLI)