ArticleNature neuroscience2019
Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output.
Article in Nature neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 359 papers, 3 of them syntheses that pooled it.
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Who cites it
359 citing papers in PubMed, 3 syntheses or guidelines pooled it, 617 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Pooled it
- A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine.Cellular oncology (Dordrecht, Netherlands) · 2025Pooled it
- Modeling human neurodegeneration with iPSCs: opportunities, limitations, and the challenge of aging.The Journal of clinical investigation · 2026Review
- Optogenetic-enabled biomanufacturing of long-projecting motor tracts for neural reconstruction.Biofabrication · 2026Article
- Stem cell derived neural organoid approaches for neurological diseases.Neural regeneration research · 2026Article
- Overcoming diffusion limits to advance brain organoids.Neural regeneration research · 2026Article
- Molecular and Proteomic Profiling of Human Cerebral Organoid‑Derived Small Extracellular Vesicles.Developmental neurobiology · 2026Article
- Tutorial: interrogating biology using organoid technologies.Nature protocols · 2026Review
- The role of impaired mitochondrial function in neurological manifestations of mitochondrial diseases.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- A reproducible three-dimensional model of human brain tissue to investigate physiological and disease-associated microglia phenotypes.Nature neuroscience · 2026Article
- Human Stem Cell-Derived Models of the Alzheimer's Disease Neuroimmune System.International journal of molecular sciences · 2026Review
- Engineering Neuronal Network Connectivity Through Precise and Scalable Electrical Modulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Modeling gliomas with organoids: Classification, fidelity, and guidelines for translational neuro-oncology.Neuro-oncology · 2026Review
- Protocol for the generation of human medullary spinal trigeminal nucleus-like organoids and trigeminothalamic assembloids.STAR protocols · 2026Article
- Brain organoids and genome editing: A new era in understanding human brain development and disorders.Neural regeneration research · 2026Article
- Neural Organoid Models as a Platform for Studying Disease Mechanisms in Amyotrophic Lateral Sclerosis.Journal of neurochemistry · 2026Review
- A human corticospinal organoid-slice connectoid model informs enhancer strategies for post-injury axon regrowth.Cell reports · 2026Article
- Mitochondrial DNA heteroplasmy drives cortical neuronal disturbances in human organoids harbouring the common m.3243A>G mutation.Nature communications · 2026Article
- Protocol for minimizing necrotic core formation in iPSC-derived cortical organoids.STAR protocols · 2026Article
299 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Neural organoids have the potential to improve our understanding of human brain development and neurological disorders. However, it remains to be seen whether these tissues can model circuit formation with functional neuronal output. Here we have adapted air-liquid interface culture to cerebral organoids, leading to improved neuronal survival and axon outgrowth. The resulting thick axon tracts display various morphologies, including long-range projection within and away from the organoid, growth-cone turning, and decussation. Single-cell RNA sequencing reveals various cortical neuronal identities, and retrograde tracing demonstrates tract morphologies that match proper molecular identities. These cultures exhibit active neuronal networks, and subcortical projecting tracts can innervate mouse spinal cord explants and evoke contractions of adjacent muscle in a manner dependent on intact organoid-derived innervating tracts. Overall, these results reveal a remarkable self-organization of corticofugal and callosal tracts with a functional output, providing new opportunities to examine relevant aspects of human CNS development and disease.
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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.