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

Human cortical organoids expose a differential function of GSK3 on cortical neurogenesis / A. Lopez-Tobon, C.E. Villa, C. Cheroni, S. Trattaro, N. Caporale, P. Conforti, R. Iennaco, M. Lachgar, M.T. Rigoli, B. Marco De La Cruz, P. Lo Riso, E. Tenderini, F. Troglio, M. De Simone, I. Liste-Noya, G. Macino, M. Pagani, E. Cattaneo, G. Testa. - In: STEM CELL REPORTS. - ISSN 2213-6711. - 13:5(2019 Nov 12), pp. 847-861.

Human cortical organoids expose a differential function of GSK3 on cortical neurogenesis

A. Lopez-Tobon;C. Cheroni;S. Trattaro;N. Caporale;P. Conforti;R. Iennaco;M.T. Rigoli;B. Marco De La Cruz;P. Lo Riso;M. De Simone;M. Pagani;E. Cattaneo;G. Testa
2019-11-12

Abstract

The regulation of the proliferation and polarity of neural progenitors is crucial for the development of the brain cortex. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator of both proliferation and polarity, yet the functional relevance of its signaling for the unique features of human corticogenesis remains to be elucidated. We harnessed human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. Single-cell transcriptome profiling revealed a direct impact on early neurogenesis and uncovered a selective role of GSK3 in the regulation of glutamatergic lineages and outer radial glia output. Our dissection of the GSK3-dependent transcriptional network in human corticogenesis underscores the robustness of the programs determining neuronal identity independent of tissue architecture.
corticogenesis; GSK3; human brain organoids; outer radial glia; single cell transcriptomics
Settore BIO/11 - Biologia Molecolare
Settore BIO/10 - Biochimica
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
Settore BIO/17 - Istologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/692986
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