Marlene F Pereira, Veronica Finazzi, Ludovico Rizzuti, Davide Aprile, Vittorio Aiello, Luca Mollica, Matteo Riva, Chiara Soriani, Francesco Dossena, Reinald Shyti, Davide Castaldi, Erika Tenderini, Maria Teresa Carminho-Rodrigues, Julien F Bally, Bert B A de Vries, Michele Gabriele, Alessandro Vitriolo, Giuseppe Testa
Germline mutations of YY1 cause Gabriele-de Vries syndrome (GADEVS), a neurodevelopmental disorder featuring intellectual disability and a wide range of systemic manifestations. To dissect the cellular and molecular mechanisms underlying GADEVS, we combined large-scale imaging, single-cell multiomics and gene regulatory network reconstruction in 2D and 3D patient-derived physiopathologically relevant cell lineages. YY1 haploinsufficiency causes a pervasive alteration of cell type specific transcriptional networks, disrupting corticogenesis at the level of neural progenitors and terminally differentiated neurons, including cytoarchitectural defects reminiscent of GADEVS clinical features...
February 17, 2024: bioRxiv