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Activin- and Nodal-related factors control antero–posterior patterning of the zebrafish embryo


Definition of cell fates along the dorso–ventral axis depends on an antagonistic relationship between ventralizing transforming growth factor-β superfamily members, the bone morphogenetic proteins1 and factors secreted from the dorsal organizer, such as Noggin and Chordin. The extracellular binding of the last group to the bone morphogenetic proteins prevents them from activating their receptors2,3,4, and the relative ventralizer:antagonist ratio is thought to specify different dorso–ventral cell fates. Here, by taking advantage of a non-genetic interference method using a specific competitive inhibitor, the Lefty-related gene product Antivin5, we provide evidence that cell fate along the antero–posterior axis of the zebrafish embryo is controlled by the morphogenetic activity of another transforming growth factor-β superfamily subgroup—the Activin and Nodal-related factors6,7,8,9. Increasing antivin doses progressively deleted posterior fates within the ectoderm, eventually resulting in the removal of all fates except forebrain and eyes. In contrast, overexpression of activin or nodal-related factors converted ectoderm that was fated to be forebrain into more posterior ectodermal or mesendodermal fates. We propose that modulation of intercellular signalling by Antivin/Activin and Nodal-related factors provides a mechanism for the graded establishment of cell fates along the antero–posterior axis of the zebrafish embryo.

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Figure 1: Dose-dependent depletion of structures along the animal–vegetal axis mediated by Antivin (Atv).
Figure 2: Dose-dependent rescue of posterior territories by Activin/Nodal-related factors.
Figure 3: Re-specification of the animal pole region into mesodermal or ectodermal structures by Nodal-related factors.

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We thank V. Heyer and T. Steffan for technical assistance and O. Nkundwa and A. Karmim for care of fish. B.T and C.T. were 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 and the Ligue Nationale Contre le Cancer. C.V.E.W. was supported by a NIH grant.

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Thisse, B., Wright, C. & Thisse, C. Activin- and Nodal-related factors control antero–posterior patterning of the zebrafish embryo. Nature 403, 425–428 (2000).

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