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The notochord is a defining feature of chordates, yet its evolutionary origin remains mysterious. Our group has identified a regulatory syntax that controls the notochordal expression of brachyury, which encodes a transcription factor essential for notochord development. This syntax is composed of binding sites of four transcription factors in a specific arrangement and is deeply conserved in diverse animals and even in a unicellular relative to animals. In chordates, it has been rewired to respond to different upstream signals, facilitating the origin of the notochord. This study reveals that during animal evolution, regulatory elements can be preserved in a specific code and repurposed for novel functions.

This study was published on July 25, 2025, in Science Advances. The first author is Tzu-Pei Fan from ICOB, with Yi-Hsien Su as the corresponding author. The research team includes Jr-Kai Yu, Che-Yi Lin, Yi-Chih Chen, Jun-Ru Lee, and collaborators Ann Cutting and Andy Cameron from California Institute of Technology. This research was supported by Academia Sinica and NSTC.