Klingler, E., Francis, F., Jabaudon, D. & Cappello, S. Mapping the molecular and cellular complexity of cortical malformations. Science 371, eaba4517 (2021).
Peng, H. et al. Morphological diversity of single neurons in molecularly defined cell types. Nature 598, 174–181 (2021).
Miyata, T. et al. Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Development 131, 3133–3145 (2004).
Noctor, S. C., Flint, A. C., Weissman, T. A., Dammerman, R. S. & Kriegstein, A. R. Neurons derived from radial glial cells establish radial units in neocortex. Nature 409, 714–720 (2001).
Noctor, S. C., Martínez-Cerdeño, V., Ivic, L. & Kriegstein, A. R. Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat. Neurosci. 7, 136–144 (2004).
Haubensak, W., Attardo, A., Denk, W. & Huttner, W. B. Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc. Natl Acad. Sci. USA 101, 3196–3201 (2004).
Fietz, S. A. et al. OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling. Nat. Neurosci. 13, 690–699 (2010).
Hansen, D. V., Lui, J. H., Parker, P. R. L. & Kriegstein, A. R. Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464, 554–561 (2010).
Bilgic, M. et al. Truncated radial glia as a common precursor in the late corticogenesis of gyrencephalic mammals. eLife 12, RP91406 (2023).
Linker, S. B. et al. Human-specific regulation of neural maturation identified by cross-primate transcriptomics. Curr. Biol. 32, 4797–4807.e5 (2022).
Libé-Philippot, B. et al. LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons. Cell 186, 5766–5783.e25 (2023).
Suzuki, I. K. et al. Human-specific NOTCH2NL genes expand cortical neurogenesis through Delta/Notch Regulation. Cell 173, 1370–1384.e16 (2018).
Florio, M. et al. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science 347, 1465–1470 (2015).
Libé-Philippot, B. et al. Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2–SYNGAP1 cross-inhibition. Neuron 112, 3602–3617.e9 (2024).
Suárez, R. et al. A pan-mammalian map of interhemispheric brain connections predates the evolution of the corpus callosum. Proc. Natl Acad. Sci. USA 115, 9622–9627 (2018).
Paolino, A. et al. Non-uniform temporal scaling of developmental processes in the mammalian cortex. Nat. Commun. 14, 5950 (2023).
Paolino, A. et al. Differential timing of a conserved transcriptional network underlies divergent cortical projection routes across mammalian brain evolution. Proc. Natl Acad. Sci. USA 117, 10554–10564 (2020).
Klingler, E. et al. Temporal controls over inter-areal cortical projection neuron fate diversity. Nature 599, 453–457 (2021).
Nowakowski, T. J. et al. The new frontier in understanding human and mammalian brain development. Nature 647, 51–59 (2025).
Klingler, E. Temporal controls over cortical projection neuron fate diversity. Curr. Opin. Neurobiol. 79, 102677 (2023).
Telley, L. et al. Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex. Science 364, eaav2522 (2019).
Bizzotto, S. & Walsh, C. A. Genetic mosaicism in the human brain: from lineage tracing to neuropsychiatric disorders. Nat. Rev. Neurosci. 23, 275–286 (2022).
Yuzwa, S. A. et al. Developmental emergence of adult neural stem cells as revealed by single-cell transcriptional profiling. Cell Rep. 21, 3970–3986 (2017).
Di Bella, D. J. et al. Molecular logic of cellular diversification in the mouse cerebral cortex. Nature 595, 554–559 (2021).
La Manno, G. et al. Molecular architecture of the developing mouse brain. Nature 596, 92–96 (2021).
Nowakowski, T. J. et al. Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex. Science 358, 1318–1323 (2017).
Bhaduri, A. et al. An atlas of cortical arealization identifies dynamic molecular signatures. Nature 598, 200–204 (2021).
Trevino, A. E. et al. Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolution. Cell 184, 5053–5069.e23 (2021).
He, Z. et al. An integrated transcriptomic cell atlas of human neural organoids. Nature 635, 690–698 (2024).
Pollen, A. A. et al. Establishing cerebral organoids as models of human-specific brain evolution. Cell 176, 743–756.e17 (2019).
Velasco, S. et al. Individual brain organoids reproducibly form cell diversity of the human cerebral cortex. Nature 570, 523–527 (2019).
Tanaka, Y., Cakir, B., Xiang, Y., Sullivan, G. J. & Park, I.-H. Synthetic analyses of single-cell transcriptomes from multiple brain organoids and fetal Brain. Cell Rep. 30, 1682–1689.e3 (2020).
Kanton, S. et al. Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature 574, 418–422 (2019).
Nowakowski, T. J., Pollen, A. A., Sandoval-Espinosa, C. & Kriegstein, A. R. Transformation of the radial glia scaffold demarcates two stages of human cerebral cortex development. Neuron 91, 1219–1227 (2016).
Fu, Y. et al. Heterogeneity of glial progenitor cells during the neurogenesis-to-gliogenesis switch in the developing human cerebral cortex. Cell Rep. 34, 108788 (2021).
Pollen, A. A. et al. Molecular identity of human outer radial glia during cortical development. Cell 163, 55–67 (2015).
Keefe, M. G., Steyert, M. R. & Nowakowski, T. J. Lineage-resolved atlas of the developing human cortex. Nature 647, 194–202 (2025).
Wang, L. et al. Molecular and cellular dynamics of the developing human neocortex. Nature 647, 169–178 (2025).
van Bruggen, D. et al. Developmental landscape of human forebrain at a single-cell level identifies early waves of oligodendrogenesis. Dev. Cell 57, 1421–1436.e5 (2022).
Rayon, T. et al. Species-specific pace of development is associated with differences in protein stability. Science 369, eaba7667 (2020).
Sherman, M. H., Bassing, C. H. & Teitell, M. A. Regulation of cell differentiation by the DNA damage response. Trends Cell Biol. 21, 312–319 (2011).
Januschke, J. & Näthke, I. Stem cell decisions: a twist of fate or a niche market? Semin. Cell Dev. Biol. 34, 116–123 (2014).
Shabani, K. et al. The temporal balance between self-renewal and differentiation of human neural stem cells requires the amyloid precursor protein. Sci. Adv. 9, eadd5002 (2023).
Schmidt, E. R. E. et al. A human-specific modifier of cortical connectivity and circuit function. Nature 599, 640–644 (2021).
Pebworth, M.-P., Ross, J., Andrews, M., Bhaduri, A. & Kriegstein, A. R. Human intermediate progenitor diversity during cortical development. Proc. Natl Acad. Sci. USA 118, e2019415118 (2021).
Rao, G. N., Katki, K. A., Madamanchi, N. R., Wu, Y. & Birrer, M. J. JunB forms the majority of the AP-1 complex and is a target for redox regulation by receptor tyrosine kinase and G protein-coupled receptor agonists in smooth muscle cells. J. Biol. Chem. 274, 6003–6010 (1999).
Aditham, A. K., Markin, C. J., Mokhtari, D. A., DelRosso, N. & Fordyce, P. M. High-throughput affinity measurements of transcription factor and DNA mutations reveal affinity and specificity determinants. Cell Syst. 12, 112–127.e11 (2021).
Lehtinen, M. K. & Walsh, C. A. Neurogenesis at the brain-cerebrospinal fluid interface. Annu. Rev. Cell Dev. Biol. 27, 653–679 (2011).
Sun, W. et al. Epigenetic regulation of human-specific gene expression in the prefrontal cortex. BMC Biol. 21, 123 (2023).
Iwata, R. & Vanderhaeghen, P. Metabolic mechanisms of species-specific developmental tempo. Dev. Cell 59, 1628–1639 (2024).
Ciceri, G. et al. An epigenetic barrier sets the timing of human neuronal maturation. Nature 626, 881–890 (2024).
Barton, R. A. & Harvey, P. H. Mosaic evolution of brain structure in mammals. Nature 405, 1055–1058 (2000).
Bystron, I., Blakemore, C. & Rakic, P. Development of the human cerebral cortex: Boulder Committee revisited. Nat. Rev. Neurosci. 9, 110–122 (2008).
Ahmed, B., Duque, A., Rakic, P. & Molnár, Z. Correlation between the number of interstitial neurons of the white matter and number of neurons within cortical layers: Histological analyses in postnatal macaque. J. Comp. Neurol. 532, e25626 (2024).
Cadwell, C. R., Bhaduri, A., Mostajo-Radji, M. A., Keefe, M. G. & Nowakowski, T. J. Development and arealization of the cerebral cortex. Neuron 103, 980–1004 (2019).
Molnár, Z. et al. New insights into the development of the human cerebral cortex. J. Anat. 235, 432–451 (2019).
Clavreul, S., Dumas, L. & Loulier, K. Astrocyte development in the cerebral cortex: complexity of their origin, genesis, and maturation. Front. Neurosci. 16, 916055 (2022).
Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888–1902.e21 (2019).
Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289–1296 (2019).
Giorgino, T. Computing and visualizing dynamic time warping alignments in R: the dtw package. J. Stat. Softw. https://doi.org/10.18637/jss.v031.i07 (2009).
Kalousis, A., Prados, J. & Hilario, M. Stability of feature selection algorithms: a study on high-dimensional spaces. Knowl. Inf. Syst. 12, 95–116 (2007).
Abe, P. et al. Molecular programs guiding arealization of descending cortical pathways. Nature 634, 644–651 (2024).
Baumann, N. et al. Regional differences in progenitor metabolism shape brain growth during development. Cell 188, 3567–3582.e20 (2025).
Biancalani, T. et al. Deep learning and alignment of spatially resolved single-cell transcriptomes with Tangram. Nat. Methods 18, 1352–1362 (2021).
Coudray, N. et al. Classification and mutation prediction from non-small cell lung cancer histopathology images using deep learning. Nat. Med. 24, 1559–1567 (2018).
Cao, J. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature 566, 496–502 (2019).
Amberger, J. S., Bocchini, C. A., Scott, A. F. & Hamosh, A. OMIM.org: leveraging knowledge across phenotype-gene relationships. Nucleic Acids Res. 47, D1038–D1043 (2019).
Corcoran, C. C., Grady, C. R., Pisitkun, T., Parulekar, J. & Knepper, M. A. From 20th century metabolic wall charts to 21st century systems biology: database of mammalian metabolic enzymes. Am. J. Physiol. 312, F533–F542 (2017).
Rath, S. et al. MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations. Nucleic Acids Res. 49, D1541–D1547 (2021).
Cabello-Aguilar, S. et al. SingleCellSignalR: inference of intercellular networks from single-cell transcriptomics. Nucleic Acids Res. 48, e55 (2020).
Lambert, S. A. et al. The human transcription factors. Cell 172, 650–665 (2018).
Greene, D., Richardson, S. & Turro, E. ontologyX: a suite of R packages for working with ontological data. Bioinformatics 33, 1104–1106 (2017).
Wu, T. et al. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation 2, 100141 (2021).
Subach, O. M., Cranfill, P. J., Davidson, M. W. & Verkhusha, V. V. An enhanced monomeric blue fluorescent protein with the high chemical stability of the chromophore. PLoS ONE 6, e28674 (2011).
Saphire, A. C., Bark, S. J. & Gerace, L. All four homochiral enantiomers of a nuclear localization sequence derived from c-Myc serve as functional import signals. J. Biol. Chem. 273, 29764–29769 (1998).
Loots, G. G. & Ovcharenko, I. rVISTA 2.0: evolutionary analysis of transcription factor binding sites. Nucleic Acids Res. 32, W217–W221 (2004).
Skelton, D., Satake, N. & Kohn, D. The enhanced green fluorescent protein (eGFP) is minimally immunogenic in C57BL/6 mice. Gene Ther. 8, 1813–1814 (2001).
Gadella, T. W. J. et al. mScarlet3: a brilliant and fast-maturing red fluorescent protein. Nat. Methods 20, 541–545 (2023).
Li, X. et al. Generation of destabilized green fluorescent protein as a transcription reporter. J. Biol. Chem. 273, 34970–34975 (1998).
Rettino, A. & Clarke, N. M. Genome-wide identification of IRF1 binding sites reveals extensive occupancy at cell death associated genes. J. Carcinog. Mutagen. https://doi.org/10.4172/2157-2518.S6-009 (2013).
Giandomenico, S. L., Sutcliffe, M. & Lancaster, M. A. Generation and long-term culture of advanced cerebral organoids for studying later stages of neural development. Nat. Protoc. 16, 579–602 (2021).
Lancaster, M. A. & Knoblich, J. A. Generation of cerebral organoids from human pluripotent stem cells. Nat. Protoc. 9, 2329–2340 (2014).
Klaus, J. et al. Altered neuronal migratory trajectories in human cerebral organoids derived from individuals with neuronal heterotopia. Nat. Med. 25, 561–568 (2019).
Buchsbaum, I. Y. et al. ECE2 regulates neurogenesis and neuronal migration during human cortical development. EMBO Rep. 21, e48204 (2020).
Valdés-Dapena, M. & Huff, D. S. Perinatal Autopsy Manual (American Registry of Pathology, 1983).
Vitali, I. et al. Progenitor hyperpolarization regulates the sequential generation of neuronal subtypes in the developing neocortex. Cell 174, 1264–1276.e15 (2018).
Liboska, R., Ligasová, A., Strunin, D., Rosenberg, I. & Koberna, K. Most anti-BrdU antibodies react with 2’-deoxy-5-ethynyluridine–the method for the effective suppression of this cross-reactivity. PLoS ONE 7, e51679 (2012).
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).
Kaya-Okur, H. S. et al. CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat. Commun. 10, 1930 (2019).
Reiff, S. B. et al. The 4D Nucleome Data Portal as a resource for searching and visualizing curated nucleomics data. Nat. Commun. 13, 2365 (2022).
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
Tarasov, A., Vilella, A. J., Cuppen, E., Nijman, I. J. & Prins, P. Sambamba: fast processing of NGS alignment formats. Bioinformatics 31, 2032–2034 (2015).
Broad Institute. Picard toolkit. GitHub https://broadinstitute.github.io/picard/ (2018).
Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).
Li, H. et al. The sequence alignment/map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
Ramírez, F. et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 44, W160–W165 (2016).
Meers, M. P., Tenenbaum, D. & Henikoff, S. Peak calling by sparse enrichment analysis for CUT&RUN chromatin profiling. Epigenetics Chromatin 12, 42 (2019).
McLean, C. Y. et al. GREAT improves functional interpretation of cis-regulatory regions. Nat. Biotechnol. 28, 495–501 (2010).
Robinson, J. T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24–26 (2011).
Bandler, R. C. et al. Single-cell delineation of lineage and genetic identity in the mouse brain. Nature 601, 404–409 (2022).
Zheng, G. X. Y. et al. Massively parallel digital transcriptional profiling of single cells. Nat. Commun. 8, 14049 (2017).
Fleming, S. J. et al. Unsupervised removal of systematic background noise from droplet-based single-cell experiments using CellBender. Nat. Methods 20, 1323–1335 (2023).
Germain, P.-L., Lun, A., Garcia Meixide, C., Macnair, W. & Robinson, M. D. Doublet identification in single-cell sequencing data using scDblFinder. F1000Research 10, 979 (2021).
Hao, Y. et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 42, 293–304 (2024).
Nestorowa, S. et al. A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation. Blood 128, e20–e31 (2016).
Kamimoto, K. et al. Dissecting cell identity via network inference and in silico gene perturbation. Nature 614, 742–751 (2023).
Liu, Y. et al. Comparative single-cell multiome identifies evolutionary changes in neural progenitor cells during primate brain development. Dev. Cell 60, 414–428.e8 (2025).
Liska, O. et al. TFLink: an integrated gateway to access transcription factor-target gene interactions for multiple species. Database 2022, baac083 (2022).
