A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification

Marios P. Stavridis, J. Simon Lunn, Barry J. Collins, Kate G. Storey

    Research output: Contribution to journalArticle

    206 Citations (Scopus)

    Abstract

    Neural tissue formation is induced by growth factors that activate networks of signal transduction cascades that ultimately lead to the expression of early neural genes, including transcription factors of the SoxB family. Here, we report that fibroblast growth factor (FGF)-induced Erk1/2 (Mapk3 and Mapk1, respectively) mitogen-activated protein kinase (MAPK), but not phosphatidylinositol 3'-OH kinase (PI3K, Pik3r1), signalling is required for neural specification in mouse embryonic stem (ES) cells and in the chick embryo. Further, blocking Erk1/2 inhibits the onset of key SoxB genes in both mouse ES cells (Sox1) and chick embryos (Sox2 and Sox3) and, in both contexts, Erk1/2 signalling is required during only a narrow time window, as neural specification takes place. In the absence of Erk1/2 signalling, differentiation of ES cells stalls following Fgf5 upregulation. Using differentiating ES cells as a model for neural specification, we demonstrate that sustained Erk1/2 activation controls the transition from an Fgf5-positive, primitive ectoderm-like cell state to a neural progenitor cell state without attenuating bone morphogenetic protein (BMP) signalling and we also define the minimum period of Erk1/2 activity required to mediate this key developmental step. Together, these findings identify a conserved, specific and stage-dependent requirement for Erk1/2 signalling downstream of FGF-induced neural specification in higher vertebrates and provide insight into the signalling dynamics governing this process.
    Original languageEnglish
    Pages (from-to)2889-94
    Number of pages6
    JournalDevelopment
    Volume134
    Issue number16
    DOIs
    Publication statusPublished - 2007

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    Fibroblast Growth Factors
    Chick Embryo
    Embryonic Stem Cells
    Phosphatidylinositol 3-Kinases
    Vertebrates
    Ectoderm
    Bone Morphogenetic Proteins
    Mitogen-Activated Protein Kinases
    Genes
    Signal Transduction
    Intercellular Signaling Peptides and Proteins
    Transcription Factors
    Up-Regulation
    Stem Cells
    Mouse Embryonic Stem Cells

    Cite this

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    title = "A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification",
    abstract = "Neural tissue formation is induced by growth factors that activate networks of signal transduction cascades that ultimately lead to the expression of early neural genes, including transcription factors of the SoxB family. Here, we report that fibroblast growth factor (FGF)-induced Erk1/2 (Mapk3 and Mapk1, respectively) mitogen-activated protein kinase (MAPK), but not phosphatidylinositol 3'-OH kinase (PI3K, Pik3r1), signalling is required for neural specification in mouse embryonic stem (ES) cells and in the chick embryo. Further, blocking Erk1/2 inhibits the onset of key SoxB genes in both mouse ES cells (Sox1) and chick embryos (Sox2 and Sox3) and, in both contexts, Erk1/2 signalling is required during only a narrow time window, as neural specification takes place. In the absence of Erk1/2 signalling, differentiation of ES cells stalls following Fgf5 upregulation. Using differentiating ES cells as a model for neural specification, we demonstrate that sustained Erk1/2 activation controls the transition from an Fgf5-positive, primitive ectoderm-like cell state to a neural progenitor cell state without attenuating bone morphogenetic protein (BMP) signalling and we also define the minimum period of Erk1/2 activity required to mediate this key developmental step. Together, these findings identify a conserved, specific and stage-dependent requirement for Erk1/2 signalling downstream of FGF-induced neural specification in higher vertebrates and provide insight into the signalling dynamics governing this process.",
    author = "Stavridis, {Marios P.} and Lunn, {J. Simon} and Collins, {Barry J.} and Storey, {Kate G.}",
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    A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification. / Stavridis, Marios P.; Lunn, J. Simon; Collins, Barry J.; Storey, Kate G.

    In: Development, Vol. 134, No. 16, 2007, p. 2889-94.

    Research output: Contribution to journalArticle

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    T1 - A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification

    AU - Stavridis, Marios P.

    AU - Lunn, J. Simon

    AU - Collins, Barry J.

    AU - Storey, Kate G.

    PY - 2007

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    AB - Neural tissue formation is induced by growth factors that activate networks of signal transduction cascades that ultimately lead to the expression of early neural genes, including transcription factors of the SoxB family. Here, we report that fibroblast growth factor (FGF)-induced Erk1/2 (Mapk3 and Mapk1, respectively) mitogen-activated protein kinase (MAPK), but not phosphatidylinositol 3'-OH kinase (PI3K, Pik3r1), signalling is required for neural specification in mouse embryonic stem (ES) cells and in the chick embryo. Further, blocking Erk1/2 inhibits the onset of key SoxB genes in both mouse ES cells (Sox1) and chick embryos (Sox2 and Sox3) and, in both contexts, Erk1/2 signalling is required during only a narrow time window, as neural specification takes place. In the absence of Erk1/2 signalling, differentiation of ES cells stalls following Fgf5 upregulation. Using differentiating ES cells as a model for neural specification, we demonstrate that sustained Erk1/2 activation controls the transition from an Fgf5-positive, primitive ectoderm-like cell state to a neural progenitor cell state without attenuating bone morphogenetic protein (BMP) signalling and we also define the minimum period of Erk1/2 activity required to mediate this key developmental step. Together, these findings identify a conserved, specific and stage-dependent requirement for Erk1/2 signalling downstream of FGF-induced neural specification in higher vertebrates and provide insight into the signalling dynamics governing this process.

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