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Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning

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Listed:
  • Sofia Sedas Perez

    (Western Bank)

  • Caitlin McQueen

    (Western Bank
    Chester Medical School)

  • Holly Stainton

    (Western Bank)

  • Joseph Pickering

    (Western Bank)

  • Kavitha Chinnaiya

    (Western Bank)

  • Patricia Saiz-Lopez

    (IBBTEC (CSIC-Universidad de Cantabria)
    Universidad de Cantabria)

  • Marysia Placzek

    (Western Bank)

  • Maria A. Ros

    (IBBTEC (CSIC-Universidad de Cantabria)
    Universidad de Cantabria)

  • Matthew Towers

    (Western Bank)

Abstract

Complex signalling between the apical ectodermal ridge (AER - a thickening of the distal epithelium) and the mesoderm controls limb patterning along the proximo-distal axis (humerus to digits). However, the essential in vivo requirement for AER-Fgf signalling makes it difficult to understand the exact roles that it fulfils. To overcome this barrier, we developed an amenable ex vivo chick wing tissue explant system that faithfully replicates in vivo parameters. Using inhibition experiments and RNA-sequencing, we identify a transient role for Fgfs in triggering the distal patterning phase. Fgfs are then dispensable for the maintenance of an intrinsic mesodermal transcriptome, which controls proliferation/differentiation timing and the duration of patterning. We also uncover additional roles for Fgf signalling in maintaining AER-related gene expression and in suppressing myogenesis. We describe a simple logic for limb patterning duration, which is potentially applicable to other systems, including the main body axis.

Suggested Citation

  • Sofia Sedas Perez & Caitlin McQueen & Holly Stainton & Joseph Pickering & Kavitha Chinnaiya & Patricia Saiz-Lopez & Marysia Placzek & Maria A. Ros & Matthew Towers, 2023. "Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41457-6
    DOI: 10.1038/s41467-023-41457-6
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    References listed on IDEAS

    as
    1. Francesca V. Mariani & Christina P. Ahn & Gail R. Martin, 2008. "Genetic evidence that FGFs have an instructive role in limb proximal–distal patterning," Nature, Nature, vol. 453(7193), pages 401-405, May.
    2. Andrew T. Dudley & María A. Ros & Clifford J. Tabin, 2002. "A re-examination of proximodistal patterning during vertebrate limb development," Nature, Nature, vol. 418(6897), pages 539-544, August.
    3. Aimée Zúñiga & Anna-Pavlina G. Haramis & Andrew P. McMahon & Rolf Zeller, 1999. "Signal relay by BMP antagonism controls the SHH/FGF4 feedback loop in vertebrate limb buds," Nature, Nature, vol. 401(6753), pages 598-602, October.
    4. Xin Sun & Francesca V. Mariani & Gail R. Martin, 2002. "Functions of FGF signalling from the apical ectodermal ridge in limb development," Nature, Nature, vol. 418(6897), pages 501-508, August.
    5. Jamie M. Verheyden & Xin Sun, 2008. "An Fgf/Gremlin inhibitory feedback loop triggers termination of limb bud outgrowth," Nature, Nature, vol. 454(7204), pages 638-641, July.
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