A 3D amphioxus brain atlas illuminates the blueprint of the ancestral chordate brain and highlights unique vertebrate innovations.

Overview

1. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
2. Biodiversity Research Center, Academia Sinica, Taipei, Taiwan
3. Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, Yilan, Taiwan

Abstract

Comparative studies of vertebrate brains have elucidated the evolution of morphological diversity; yet, the fundamental chordate brain blueprint and the emergence of vertebrate-specific innovations remain elusive. To reconstruct the cellular and molecular origins of brain architecture in chordates, we combined single-nucleus RNA sequencing with spatial transcriptomics to generate a three-dimensional cell atlas of the central nervous system (CNS) in the early-branching chordate amphioxus. This atlas reveals a tripartite anterior-posterior organization comprising a rostral retinal/hypothalamic region, a di-mesencephalic domain, and a caudal hindbrain/spinal cord. Challenging previous views, we identify cell clusters resembling the vertebrate zona limitans intrathalamica and midbrain-hindbrain boundary regions that demarcate major brain compartments. Conversely, the absence of telencephalic marker expression in the amphioxus rostral forebrain suggests that the telencephalon is a vertebrate innovation. Collectively, our findings establish a spatial transcriptomic framework for the amphioxus CNS, providing crucial insight into the evolutionary origins of vertebrate brain complexity.

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Data

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• geo:GSE327901, at NCBI GEO; found in “Data, code, and materials availability:”

Data, code, and materials availability

All data and code needed to evaluate and reproduce the results in the paper are present in the paper and/or the Supplementary Materials. Raw sequencing data have been deposited in the NCBI database under BioProject PRJNA1369173. Xenium data have been deposited in the Gene Expression Omnibus (GEO) under accession number GSE327901 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327901). The custom code used in this study is publicly available on GitHub (https://github.com/LCY-ICOB/amphiBrain) and Zenodo (https://zenodo.org/records/19658940). Mouse scRNA-seq data (33) were downloaded from http://mousebrain.org. Mouse in situ hybridization data were retrieved from the Allen Mouse Brain Atlas (81) (https://mouse.brain-map.org/static/atlas). Zebrafish scRNA-seq data (36, 37) were retrieved from the GEO under accession numbers GSE112294 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112294) and GSE105010 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE105010). This study did not generate new materials.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

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Version 2, 28 September 2026

• Funding: added Academia Sinica: AS-GC-111-L01

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 8 MeSH terms, 73 references.

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This paper

Lin, C.-Y., Hsu, W.-H., Lu, M.-Y. J., Chen, Y.-H., Li, K.-L., Chen, Y.-C., Su, Y.-H., Chou, S.-J., & Yu, J.-K. (2026). A 3D amphioxus brain atlas illuminates the blueprint of the ancestral chordate brain and highlights unique vertebrate innovations. Science advances, 12(27), eaee5076. https://doi.org/10.1126/sciadv.aee5076

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