Based on grafting experiments, Mangold and Spemann showed the dorsal blastopore lip of an amphibian gastrula to be able to induce a secondary body axis1. The equivalent of this organizer region has been identified in different vertebrates including teleosts2. However, whereas the graft can induce ectopic head and trunk, endogenous and ectopic axes fuse in the posterior part of the body3,4, raising the question of whether a distinct organizer region is necessary for tail development. Here we reveal, by isochronic and heterochronic transplantation, the existence of a tail organizer deriving from the ventral margin of the zebrafish embryo, which is independent of the dorsal Spemann organizer. Loss-of-function experiments reveal that bone morphogenetic protein (BMP), Nodal and Wnt8 signalling pathways are required for tail development. Moreover, stimulation of naive cells by a combination of BMP, Nodal and Wnt8 mimics the tail-organizing activity of the ventral margin and induces surrounding tissues to become tail. In contrast to induction of the vertebrate head, known to result from the triple inhibition of BMP, Nodal and Wnt5, here we show that induction of the tail results from the triple stimulation of BMP, Nodal and Wnt8 signalling pathways.
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We thank V. Heyer for technical assistance, C. Hindelang for histology and A. Goupilleau for care of the fish. We also thank M. Fürthauer for discussion, N. Ueno for the gift of the CA-BRIA clone and M. Halpern for the fish strains. This work was supported by funds from the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique, the Hôpital Universitaire de Strasbourg, the Association pour la Recherche sur le Cancer, the Ligue Nationale Contre le Cancer and the National Institute of Health. A.A. is a recipient of the Ministère de l'Education Nationale et de la Recherche.
The authors declare that they have no competing financial interests.
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Agathon, A., Thisse, C. & Thisse, B. The molecular nature of the zebrafish tail organizer. Nature 424, 448–452 (2003). https://doi.org/10.1038/nature01822
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