Dynamic behaviour of human neuroepithelial cells in the developing forebrain

Abstract

To understand how diverse progenitor cells contribute to human neocortex development, we examined forebrain progenitor behaviour using timelapse imaging. Here we find that cell cycle dynamics of human neuroepithelial (NE) cells differ from radial glial (RG) cells in both primary tissue and in stem cell-derived organoids. NE cells undergoing proliferative, symmetric divisions retract their basal processes, and both daughter cells regrow a new process following cytokinesis. The mitotic retraction of the basal process is recapitulated by NE cells in cerebral organoids generated from human-induced pluripotent stem cells. In contrast, RG cells undergoing vertical cleavage retain their basal fibres throughout mitosis, both in primary tissue and in older organoids. Our findings highlight developmentally regulated changes in mitotic behaviour that may relate to the role of RG cells to provide a stable scaffold for neuronal migration, and suggest that the transition in mitotic dynamics can be studied in organoid models.

An early cell shape transition drives evolutionary expansion of the human forebrain

“…We also tracked individual NE cells by live imaging in order to see how cell shape differences between species might arise before day 5 (Movie S1, S2). As previously observed in human NE cells (Subramanian et al, 2017), we observed a transient loss of the basal process during NE cell division in both human and gorilla. Following the division, NE daughter cells in both species initially displayed a thinner apical process than the parent cell.…”

mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex

“…Cortical organoids, therefore, present an attractive option for future exploration as they are stem cell-derived, can be maintained long term, and are well-suited for molecular and genetic manipulations. While cortical organoids do not currently replicate all aspects of developing cortical organization and metabolism (Amiri et al, 2018;Bhaduri et al, 2020;Camp et al, 2015;Pollen et al, 2019), many molecular and cellular developmental programs are conserved Lancaster et al, 2013;Quadrato et al, 2017;Sloan et al, 2017;Subramanian et al, 2017;Velasco et al, 2019). In this study, we demonstrate that the mTOR signaling pathway has similar expression and functional effects in both primary human tissue and organoids.…”

Cortical Malformations: Lessons in Human Brain Development

“…These NE cells are arranged in a pseudostratified epithelial organization with apical and basal contacts. Early on in development, NE cells proliferate symmetrically to generate more NE cells and expand the progenitor pool (Subramanian et al, 2017). This expansion of the NE progenitors has been hypothesized to be one of the key factors that contribute to an increased number of progenitor cells in the human brain (Rakic, 2009).…”