Intrinsic properties of limb bud cells can be differentially reset

Development. 2017 Feb 1;144(3):479-486. doi: 10.1242/dev.137661. Epub 2017 Jan 13.


An intrinsic timing mechanism specifies the positional values of the zeugopod (i.e. radius/ulna) and then autopod (i.e. wrist/digits) segments during limb development. Here, we have addressed whether this timing mechanism ensures that patterning events occur only once by grafting GFP-expressing autopod progenitor cells to the earlier host signalling environment of zeugopod progenitor cells. We show by detecting Hoxa13 expression that early and late autopod progenitors fated for the wrist and phalanges, respectively, both contribute to the entire host autopod, indicating that the autopod positional value is irreversibly determined. We provide evidence that Hoxa13 provides an autopod-specific positional value that correctly allocates cells into the autopod, most likely through the control of cell-surface properties as shown by cell-cell sorting analyses. However, we demonstrate that only the earlier autopod cells can adopt the host proliferation rate to permit normal morphogenesis. Therefore, our findings reveal that the ability of embryonic cells to differentially reset their intrinsic behaviours confers robustness to limb morphogenesis. We speculate that this plasticity could be maintained beyond embryogenesis in limbs with regenerative capacity.

Keywords: Chick; Hoxa13; Limb development; Proliferation; Proximo-distal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Avian Proteins / genetics
  • Avian Proteins / metabolism
  • Body Patterning
  • Cell Cycle Checkpoints
  • Cell Lineage
  • Chick Embryo
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / transplantation
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Limb Buds / cytology*
  • Limb Buds / embryology*
  • Limb Buds / metabolism
  • Regeneration
  • Wings, Animal / cytology
  • Wings, Animal / embryology
  • Wings, Animal / metabolism


  • Avian Proteins
  • Homeodomain Proteins
  • homeobox protein HOXA13