Summary: An international team has produced a detailed blueprint of the human neocortex — the outer layer of the brain responsible for higher cognition, decision-making, and sensory processing.
By integrating data from nearly 200 studies and more than 30 million individual cells, researchers assembled a fine-grained atlas that traces neocortical development from prenatal stages through adulthood. This open-access resource enables scientists to identify precisely when and where typical developmental trajectories diverge, offering new leads on the origins of conditions such as autism, microcephaly, and Alzheimer’s disease.
Key Facts
- The Neocortex Engine: The atlas documents the cellular transitions and gene expression programs that underlie the extraordinary expansion of the human neocortex compared with other mammals.
- Extended Human Maturation: Neurons in humans require years to reach full maturity, whereas comparable processes in mice complete in weeks. This prolonged developmental window supports complex learning and social adaptation.
- Focused Gene Programs: Evolution concentrated ancient, diffuse gene networks into specialized programs within human neural stem cells, helping drive neocortical growth and advanced cognitive capacity.
- Open-Access Utility: The data are available through a user-friendly portal that allows researchers without coding experience to explore gene modules and accelerate the search for targeted therapies for neurodevelopmental disorders.
Source: Johns Hopkins Medicine
Overview: Researchers at Johns Hopkins Medicine and collaborators worldwide have been building a molecular map of the human brain to better understand—and ultimately treat—disorders that affect early cognition, development, and brain health later in life.
Supported by federal and international grants, these models help investigators examine genetic pathways implicated in a spectrum of conditions, from autism spectrum disorder, which affects roughly 3% of children in the U.S., to Alzheimer’s disease, which impacts millions of older adults.
Carlo Colantuoni, Ph.D., adjunct professor of neurology at Johns Hopkins Medicine and the Institute for Genome Sciences at the University of Maryland School of Medicine, led the effort to synthesize data from nearly 200 published studies and over 30 million cells into a comprehensive portrait of neocortical development. The resulting atlas reveals how the outermost brain layers form, specialize, and mature through life.
The neocortex supports many human capacities, including thinking, sensing, memory formation, and decision-making. “Our aim is to understand how the neocortex is assembled at the cellular level and to uncover clues about the earliest signs of developmental delays and brain disorders,” Colantuoni said. “Mapping the cellular transitions and gene programs that build the neocortex is a prerequisite for developing interventions that could target conditions that begin in utero, emerge during childhood, or appear later in life.”
Beyond autism, the atlas offers insight into rare developmental disorders such as microcephaly, where impaired brain growth can begin before birth and have profound effects on brain structure and function.
Published in Nature and Nature Neuroscience, the study provides not only a human neocortical model but also comparative atlases for other mammals and mice. These comparisons show that gene expression programs once distributed across many cell types became concentrated in human neural stem cells over evolutionary time, a change that helped drive neocortical expansion and contributed to differences in higher cognitive abilities among species.
The researchers also charted the tempo of neuronal maturation in the human neocortex. They found that neuronal development has become protracted in humans: processes that unfold in weeks in mice take many years in people. This extended maturation enables the human brain to adapt over a long developmental window to complex social, sensory, and environmental inputs.
The atlas and its associated tools are available as an open-access web portal to support other scientists studying brain development and neurological disease. Colantuoni notes that this collective resource is designed to facilitate investigation of disease mechanisms across the lifespan and to accelerate routine research by providing ready access to harmonized transcriptomic data.
The portal allows researchers without programming skills to inspect expression patterns of individual genes, examine coordinated gene modules active during specific developmental stages, and contribute new datasets to expand the resource.
These efforts build on previous initiatives such as the BRAIN Initiative, which generated comprehensive cell censuses for human and mouse brains, and on broader projects like the Human Cell Atlas that aim to map every cell type in the body. Work from these consortia has already identified new lung cell types, clarified immune responses to infection, and revealed cellular networks that coordinate cardiac function.
“We are in an unprecedented era for integrating technology, large datasets, and international collaboration to discover treatments that can save and improve lives,” Colantuoni said. He emphasized the importance of continued participation from academic and industry partners to expand these precompetitive data resources and to identify novel molecular targets for brain disorders.
He and colleagues believe that combining these atlases with AI-guided screening in stem cell systems will enable precision therapies tailored to individual patients with neurodevelopmental or neurodegenerative disease.
To advance this vision, Colantuoni and collaborators — including Paul Worley, Jin-Chong Xu, Xiangyu Liao, Yuelin Lao, Carol A. Barnes, Matthew Huetelman, and Ignazio S. Piras — have also assembled an open dataset focused on Alzheimer’s disease.
Other contributors to the neocortical development study include Shreyash Sonthalia, Ricky S. Adkins, Joshua Orvis, Guangyan Li, Xoel Mato Blanco, Alex Casella, Jinrui Liu, Genevieve Stein-O’Brien, Brian Caffo, Ronna Hertzano, Anup Mahurkar, Jesse Gillis, Jonathan Werner, Shaojie Ma, Nicola Micali, Nenad Sestan, Pasko Rakic, Gabriel Santpere, and Seth A. Ament.
Funding: The work was supported by multiple federal and international grants, including PTE federal awards and NIH grants listed in the original report, as well as awards from international agencies and the Johns Hopkins University Discovery Award. The authors report no disclosures.
Key Questions Answered:
A: This extended development is an evolutionary survival feature: unlike a mouse brain that matures in weeks, human neuronal maturation unfolds over years. That prolonged period provides a large window for learning, adaptation, and the acquisition of complex social and cognitive skills.
A: By offering a detailed map of healthy neocortical development, scientists can identify exact points where development diverges in conditions like autism or Alzheimer’s. This precision makes it possible to target specific gene modules and molecular pathways in the pursuit of more effective, individualized therapies.
A: While this project centers on the neocortex, it is part of a broader effort to map human cell types across the body. Related initiatives have already uncovered new lung cell types, clarified mechanisms of infection response, and mapped cell networks that support heart function.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full.
- Additional context was added by editorial staff.
About this neurology and aging research news
Author: Jessica Frost
Source: Johns Hopkins Medicine
Contact: Jessica Frost – Johns Hopkins Medicine
Image: Image credited to Neuroscience News
Original Research: Open access. “A Curated Compendium of Transcriptomic Data for the Exploration of Neocortical Development” by Shreyash Sonthalia et al., published in Nature Neuroscience. DOI: 10.1038/s41593-026-02204-4
Abstract
A Curated Compendium of Transcriptomic Data for the Exploration of Neocortical Development
To enable researchers to harness the combined discovery potential of public multiomic datasets, the authors collected gene-level transcriptomic data from approximately 200 studies of neocortical development and related in vitro models. Using joint matrix decomposition across mouse, macaque, and human data, they identified conserved transcriptomic dynamics during neocortical neurogenesis and a program emerging in ventricular progenitors that later appears in primate outer radial glia but is limited to glial precursors in rodents.
Decomposition of adult human neocortical data revealed layer-specific signatures in excitatory neurons, allowing researchers to chart their developmental emergence and prolonged maturation, which contrasts with the early peak expression of layer-defining transcription factors. Analysis of cerebral organoid data showed that while many broad aspects of in vivo development are recapitulated in vitro, several layer-specific transcriptional programs of neuronal maturation are absent.
The authors invite cell biologists and other researchers to use NeMO Analytics to explore these data and to contribute new datasets to expand the resource for the community.