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An intrinsic cell cycle timer terminates limb bud outgrowth.

Joseph Pickering1, Constance A Rich1, Holly Stainton1

  • 1Department of Biomedical Science, The Bateson Centre, University of Sheffield, Sheffield, United Kingdom.

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|September 4, 2018
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Limb development outgrowth termination is controlled by an intrinsic cell cycle timer, not extrinsic signaling breakdown. This timer requires epithelial-mesenchymal signaling permissively to regulate limb growth.

Keywords:
chickendevelopmental biologygrowthlimbtiming

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Area of Science:

  • Developmental biology
  • Cell cycle regulation
  • Limb development

Background:

  • Proliferative outgrowth in limb development traditionally ends with the breakdown of epithelial-mesenchymal (e-m) signaling.
  • The precise mechanisms governing the termination of limb bud growth remain incompletely understood.

Purpose of the Study:

  • To investigate the role of extrinsic epithelial-mesenchymal signaling in terminating limb bud proliferative outgrowth.
  • To elucidate the underlying mechanisms controlling the cessation of cell proliferation during limb development.

Main Methods:

  • Grafting experiments using late-stage chick wing bud mesenchyme into younger wing bud epithelia.
  • RNA sequencing to analyze gene expression changes in distal mesenchyme cells.
  • Investigating the role of Bone Morphogenetic Protein (BMP) signaling pathways.

Main Results:

  • Epithelial-mesenchymal (e-m) signaling breakdown is not required for proliferative outgrowth termination.
  • Distal mesenchyme cells possess an intrinsic cell cycle timer that dictates outgrowth cessation.
  • E-m signaling acts permissively, allowing the intrinsic timer to regulate cell proliferation.
  • A switch from BMP antagonism to BMP signaling controls this intrinsic timer.

Conclusions:

  • Limb development outgrowth termination is primarily regulated by an intrinsic cell cycle timer within the mesenchyme.
  • Epithelial-mesenchymal signaling plays a permissive role, rather than a termination signal, in this process.
  • Findings suggest a conserved mechanism integrating extrinsic signals and intrinsic timers in developmental patterning systems.