Spatial waves and temporal oscillations in vertebrate limb development

Biosystems. 2021 Oct:208:104502. doi: 10.1016/j.biosystems.2021.104502. Epub 2021 Aug 5.


The mesenchymal tissue of the developing vertebrate limb bud is an excitable medium that sustains both spatial and temporal periodic phenomena. The first of these is the outcome of general Turing-type reaction-diffusion dynamics that generate spatial standing waves of cell condensations. These condensations are transformed into the nodules and rods of the cartilaginous, and eventually (in most species) the bony, endoskeleton. In the second, temporal periodicity results from intracellular regulatory dynamics that generate oscillations in the expression of one or more gene whose products modulate the spatial patterning system. Here we review experimental evidence from the chicken embryo, interpreted by a set of mathematical and computational models, that the spatial wave-forming system is based on two glycan-binding proteins, galectin-1A and galectin-8 in interaction with each other and the cells that produce them, and that the temporal oscillation occurs in the expression of the transcriptional coregulator Hes1. The multicellular synchronization of the Hes1 oscillation across the limb bud serves to coordinate the biochemical states of the mesenchymal cells globally, thereby refining and sharpening the spatial pattern. Significantly, the wave-forming reaction-diffusion-based mechanism itself, unlike most Turing-type systems, does not contain an oscillatory core, and may have evolved to this condition as it came to incorporate the cell-matrix adhesion module that enabled its pattern-forming capability.

Keywords: Galectin; Limb skeletogenesis; Lyapunov function; Morphogenetic field; Reaction-diffusion.

MeSH terms

  • Animals
  • Biological Clocks / physiology*
  • Diffusion
  • Extremities / growth & development*
  • Humans
  • Periodicity*
  • Time Factors
  • Vertebrates