Neural induction is the process through which pluripotent cells are committed to a neural fate. This first step of central nervous system formation is triggered by the ‘Spemann organizer’ in amphibians and by homologous embryonic regions in other vertebrates. Studies in classical vertebrate models have produced contrasting views about the molecular nature of neural inducers and no unifying scheme could be drawn. Moreover, how this process evolved in the chordate lineage remains unresolved. Here we show, by using graft and micromanipulation experiments, that the dorsal blastopore lip of the cephalochordate amphioxus is homologous to the vertebrate organizer and is able to trigger the formation of neural tissues in a host embryo. In addition, we demonstrate that Nodal–Activin is the main signal eliciting neural induction in amphioxus, and that it also functions as a bona fide neural inducer in the classical vertebrate model Xenopus. Together, our results allow us to propose that Nodal–Activin was a major factor for neural induction in the ancestor of chordates. This study further reveals the diversity of neural inducers used during chordate evolution and provides support against a universally conserved molecular explanation for this process.
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The laboratory of H.E. was supported by the CNRS and the ANR-16-CE12-0008-01 and S.B. was supported by the Institut Universitaire de France. This project was supported in L.K.’s laboratory by ANR BSV2-021-02 and by Fondation ARC. M.I. is supported by an ERC Starting Grant (grant agreement ERC-StG-LS2-637591) and the Spanish Ministry of Economy and Competitiveness (‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208 to the CRG). Some of the Xenopus experiments were performed in the PiCSL-FBI core facility (IBDM, AMU-Marseille), member of the France-BioImaging national research infrastructure. Some of the amphioxus experiments were carried out on the Cytometry and Imaging Platform of the Observatoire Océanologique de Banyuls-sur-Mer. RNA sequencing was performed at the CRG Genomics facility. We thank S. Darras for technical help and M. Belgacem for amphioxus FGF1/2 in vitro production.
The authors declare no competing financial interests.
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Le Petillon, Y., Luxardi, G., Scerbo, P. et al. Nodal–Activin pathway is a conserved neural induction signal in chordates. Nat Ecol Evol 1, 1192–1200 (2017). https://doi.org/10.1038/s41559-017-0226-3
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