Human Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesis

• DOI: 10.1016/j.stemcr.2019.09.005
• Publication Date: 2019-10-10T18:05:10Z
• Authors: Alejandro López-T...; Carlo Emanuele Villa; Cristina Cheroni; Sebastiano Trattaro; Nicolò Caporale; Paola Conforti; Raffaele Iennaco; Maria Lachgar; Marco Tullio Rigoli; Berta Marcó de la...; Pietro Lo Riso; Erika Tenderini; Flavia Troglio; Marco De Simone; Isabel Liste-Noya; Giuseppe Macino; Massimiliano Pagani; Elena Cattaneo; Giuseppe Testa
• Keywords: Corticogenesis; Organoid; Neuroectoderm; Human brain

The regulation of the proliferation and polarity neural progenitors is crucial for development brain cortex. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator both polarity, yet functional relevance its signaling unique features human corticogenesis remains to be elucidated. We harnessed cortical organoids probe longitudinal impact GSK3 inhibition through multiple developmental stages. Chronic increased caused massive derangement tissue architecture. Single-cell transcriptome profiling revealed direct on early neurogenesis uncovered selective role in glutamatergic lineages outer radial glia output. Our dissection GSK3-dependent transcriptional network underscores robustness programs determining neuronal identity independent