An intrinsic timer specifies distal structures of the vertebrate limb

Nat Commun. 2015 Sep 18:6:8108. doi: 10.1038/ncomms9108.

Abstract

How the positional values along the proximo-distal axis (stylopod-zeugopod-autopod) of the limb are specified is intensely debated. Early work suggested that cells intrinsically change their proximo-distal positional values by measuring time. Recently, however, it is suggested that instructive extrinsic signals from the trunk and apical ectodermal ridge specify the stylopod and zeugopod/autopod, respectively. Here, we show that the zeugopod and autopod are specified by an intrinsic timing mechanism. By grafting green fluorescent protein-expressing cells from early to late chick wing buds, we demonstrate that distal mesenchyme cells intrinsically time Hoxa13 expression, cell cycle parameters and the duration of the overlying apical ectodermal ridge. In addition, we reveal that cell affinities intrinsically change in the distal mesenchyme, which we suggest results in a gradient of positional values along the proximo-distal axis. We propose a complete model in which a switch from extrinsic signalling to intrinsic timing patterns the vertebrate limb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bones of Upper Extremity / embryology
  • Bones of Upper Extremity / metabolism
  • Cell Cycle
  • Chick Embryo
  • Ectoderm / embryology
  • Ectoderm / metabolism
  • Extremities / embryology
  • Fibroblast Growth Factors / metabolism*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Time Factors
  • Wings, Animal / embryology*
  • Wings, Animal / metabolism

Substances

  • Homeodomain Proteins
  • green fluorescent protein, Aequorea victoria
  • homeobox protein HOXA13
  • Green Fluorescent Proteins
  • Fibroblast Growth Factors