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fgf8 mRNA decay establishes a gradient that couples axial elongation to patterning in the vertebrate embryo

Abstract

Formation and patterning of the vertebrate embryo occur in a head-to-tail sequence. This progressive mode of body formation from the posterior end of the embryo requires a strict temporal coordination of tissue differentiation—a process involving fibroblast growth factor (FGF) signalling. Here we show that transcription of fgf8 messenger RNA is restricted to the growing posterior tip of the embryo. fgf8 mRNA is progressively degraded in the newly formed tissues, resulting in the formation of an mRNA gradient in the posterior part of the embryo. This fgf8 mRNA gradient is translated into a gradient of FGF8 protein, which correlates with graded phosphorylation of the kinase Akt, a downstream effector of FGF signalling. Such a mechanism provides an efficient means to monitor the timing of FGF signalling, coupling the differentiation of embryonic tissues to the posterior elongation of the embryo. In addition, this mechanism provides a novel model for morphogen gradient formation.

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Figure 1: Characterization of the posterior gradient of fgf8 mRNA and FGF8 protein.
Figure 2: Expression of fgf8 is not regulated by extrinsic signals.
Figure 3: fgf8 mRNA is only transcribed at the tail-bud level of mouse and chick embryos.
Figure 4: High stability of processed fgf8 mRNAs.
Figure 5: Two different mechanisms of establishing a protein gradient.

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Acknowledgements

We thank D. Duboule for discussions; G. Martin for reagents; B. Brede for help with real-time PCR; S. Fraser , D. Ish-Horowicz, P Kulesa, T. Lecuit and members of the Pourquié laboratory for comments on the manuscript. J.D. was a recipient of a fellowship from the Fondation pour la Recherche Medicale (FRM). This work was initiated in the Laboratoire of Genetique et Physiologie du Developpement in Marseille, supported by funding from the Centre National de le Recherche Scientifique (CNRS), Human Frontier Science Program Organization (HFSPO), Association Francaise contre les Myopathies and the Université de la Méditerranée-AP de Marseille. Current work is supported by the Stowers Institute and a grant from the NIH.

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Correspondence to Olivier Pourquié.

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41586_2004_BFnature02216_MOESM1_ESM.jpg

Supplementary Figure 1: Salt and pepper expression of fgf8 mRNA in the caudal PSM. Sagittal section through the caudal PSM of the chick embryo hybridized with fgf8 shown in 1e. (JPG 51 kb)

Supplementary Figure Legend (DOC 19 kb)

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Dubrulle, J., Pourquié, O. fgf8 mRNA decay establishes a gradient that couples axial elongation to patterning in the vertebrate embryo. Nature 427, 419–422 (2004). https://doi.org/10.1038/nature02216

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