PLX209069

GSE153076: An early cell shape transition drives evolutionary expansion of human forebrain

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

The human brain has undergone rapid expansion since humans diverged from other great apes, but the mechanism of this human-specific enlargement is still unknown. Here, we use cerebral organoids derived from human, gorilla and chimpanzee cells to study developmental mechanisms driving evolutionary brain expansion. We find that the differentiation of neuroepithelial cells to neurogenic radial glia is a protracted process in apes, involving a previously unrecognized transition state characterized by a change in cell shape. Furthermore, we show that human organoids are larger due to a delay in this transition. Temporally resolved RNA-seq from human and gorilla organoids reveals differences in gene expression patterns associated with cell morphogenesis, and in particular highlight ZEB2, a known regulator of epithelial-mesenchymal transition and cell shape. We show, through loss- and gain-of-function experiments, that ZEB2 promotes the progression of neuroepithelial differentiation, and its ectopic overexpression in human is sufficient to trigger a premature transition. By mimicking the nonhuman ape expression of this human evolution gene, we are able to force the acquisition of nonhuman ape architecture in human organoids, establishing for the first time, an instructive role of neuroepithelial cell shape in human brain expansion. SOURCE: Paula Freire Pritchett (paulafp@mrc-lmb.cam.ac.uk) - Medical Research Council