Journal Article

A cell fate decision map reveals abundant direct neurogenesis bypassing intermediate progenitors in the human developing neocortex

Attie-Bitach, Tania, Brunet Avalos, Clarisse, Wimmer, Ryszard, Baffet, Alexandre, Bessières, Betina, Guimiot, Fabien, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Farcy, Sarah, Fraisier, Vincent, Di Cicco, Amandine, Sens, Pierre, Lampic, Marusa, AP-HP Hôpital universitaire Robert-Debré, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), BioImaging Cell and Tissue Core Facility (PICT-IBiSA), Macé, Anne-Sophie, Brault, Jean-Baptiste, Biologie Cellulaire et Cancer, Hôpital Necker - Enfants Malades, Coquand, Laure, Physique des Cellules et Cancer = Physics of Cells and Cancer (PCC)

2024

Overview

Abstract The human neocortex has undergone strong evolutionary expansion, largely due to an increased progenitor population, the basal radial glial cells. These cells are responsible for the production of a diversity of cell types, but the successive cell fate decisions taken by individual progenitors remain unknown. Here we developed a semi-automated live/fixed correlative imaging method to map basal radial glial cell division modes in early fetal tissue and cerebral organoids. Through the live analysis of hundreds of dividing progenitors, we show that basal radial glial cells undergo abundant symmetric amplifying divisions, and frequent self-consuming direct neurogenic divisions, bypassing intermediate progenitors. These direct neurogenic divisions are more abundant in the upper part of the subventricular zone. We furthermore demonstrate asymmetric Notch activation in the self-renewing daughter cells, independently of basal fibre inheritance. Our results reveal a remarkable conservation of fate decisions in cerebral organoids, supporting their value as models of early human neurogenesis.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK
• Subject: 631/136/368/2430 / 631/532/2182 / Amplification / Biomedical and Life Sciences / Cancer Research / Cell Biology / Cell Differentiation / Cell Division / Cell fate / Cell Lineage / Cell Proliferation / Cerebral cortex / Decisions / Developmental Biology / Ependymoglial Cells - cytology / Ependymoglial Cells - metabolism / Fetuses / Glial cells / Humans / Life Sciences / Neocortex / Neocortex - cytology / Neocortex - embryology / Neocortex - metabolism / Neural Stem Cells - cytology / Neural Stem Cells - metabolism / Neurogenesis / Neuroglia / Organoids / Organoids - cytology / Organoids - metabolism / Radial glial cells / Receptors, Notch - genetics / Receptors, Notch - metabolism / Stem Cells / Subventricular zone