ArticleCell2021
An early cell shape transition drives evolutionary expansion of the human forebrain.
Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 2 of them syntheses that pooled it.
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Who cites it
153 citing papers in PubMed, 2 syntheses or guidelines pooled it, 256 citations in OpenAlex.
- Meta-analysis of single-cell RNA sequencing co-expression in human neural organoids reveals their high variability in recapitulating primary tissue.PLoS biology · 2024Pooled it
- Building on a Solid Foundation: Adding Relevance and Reproducibility to Neurological Modeling Using Human Pluripotent Stem Cells.Frontiers in cellular neuroscience · 2021Pooled it
- Human-specific morphoregulatory signatures in basal radial glia characterise neocortex evolution.Nature communications · 2026Article
- CCNB1IP1 regulatory evolution underlies gradual increases in cortical size and folding in primates.Nature genetics · 2026Article
- Coordinated neural progenitor adaptations contribute to primate neocortical downscaling.Science advances · 2026Article
- Tutorial: interrogating biology using organoid technologies.Nature protocols · 2026Review
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- Morphogen-Directed, High-Throughput Development of hiPSC-Derived Telencephalic Organoids for Comparative In Vitro Phenotyping.Current protocols · 2026Article
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- Reversible epiblast regionalization determines differentiation potential of human pluripotent stem cells.Nature biotechnology · 2026Article
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- Developmental signaling reveals functionally enriched human-specific gene regulation in telencephalic progenitors.bioRxiv : the preprint server for biology · 2026Article
- Light- and chemical-induced ciliary signaling governs dorsal/ventral regionalization of human telencephalic organoids.Nature communications · 2026Article
- A LINE-1 insertion upstream of FOXP2 promotes neuronal differentiation during primate evolution.Genome biology · 2026Article
- Genomic approaches for understanding the evolution of the human brain.Nature neuroscience · 2026Review
- CrossFilt: a cross-species filtering tool that eliminates alignment bias in comparative genomics studies of primates.Genome biology · 2026Article
- FABP7 controls radial glial scaffold stability during human cortical development.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- How human-derived brain organoids are built differently from brain organoids derived from genetically-close relatives: a multi-scale hypothesis.Soft matter · 2026Article
- Unraveling the Morphological and Functional Maturation Mechanisms Underlying Human Neural Development Using iPSCs-Derived Neuronal Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
93 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
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 neuroepithelial differentiation 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, associated with differences in interkinetic nuclear migration and cell cycle length. Comparative RNA sequencing (RNA-seq) reveals differences in expression dynamics of cell morphogenesis factors, including ZEB2, a known epithelial-mesenchymal transition regulator. We show that ZEB2 promotes neuroepithelial transition, and its manipulation and downstream signaling leads to acquisition of nonhuman ape architecture in the human context and vice versa, establishing an important role for neuroepithelial cell shape in human brain expansion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.