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How did the highly complex vertebrate brain evolve from a simple ancestral blueprint? A new study now brings scientists significantly closer to answering this longstanding question. In a recent study published in Science Advances, a research team led by Research Fellow Jr-Kai Yu and Postdoctoral Fellow Che-Yi Lin from the Institute of Cellular and Organismic Biology at Academia Sinica has constructed a spatially resolved cell-type atlas of the adult amphioxus brain, unveiling the deep ancestry of our own central nervous system.

Amphioxus, an early-branching invertebrate chordate, occupies a pivotal position in chordate evolution, making it an ideal model for tracing the origins of the vertebrate brain. By combining single-nucleus RNA sequencing with spatial transcriptomics, the team showed that the amphioxus brain shares a conserved tripartite organization with vertebrates. This structural blueprint features molecular boundaries similar to key vertebrate brain organizers—the zona limitans intrathalamica (ZLI) and the midbrain-hindbrain boundary (MHB)—challenging long-held assumptions that these critical developmental landmarks were missing in amphioxus.

The high-resolution atlas serves as a three-dimensional blueprint of the amphioxus brain, revealing tens of thousands of neurons and their cell types, functions, and locations within the brain. Crucially, it revealed the absence of key telencephalic marker expression in the amphioxus forebrain, suggesting that the telencephalon—the region driving complex cognitive processing—is a unique vertebrate innovation rather than an inherited ancestral trait. Beyond this technical milestone, the research team established a critical phylogenetic baseline for chordate neuroanatomy. By successfully separating ancient, conserved features from evolutionary novelties, this research provides an important reference for future comparative studies of brain evolution across species.

This study was supported by the Academia Sinica Grand Challenge Program and research grants from the National Science and Technology Council of Taiwan. Crucial technical assistance was provided by the High-Throughput Genomics Core Facility at the Biodiversity Research Center, Academia Sinica. The co-authors are Wen-Hsin Hsu, Mei-Yeh Jade Lu, Yi-Hua Chen, Kun-Lung Li, Yi-Chih Chen, Yi-Hsien Su, and Shen-Ju Chou.

Article link: https://www.science.org/doi/10.1126/sciadv.aee5076