Spatial waves and temporal oscillations in vertebrate limb development

Stuart A Newman,Ramray Bhat,Tilmann Glimm

doi:10.1016/j.biosystems.2021.104502

Stuart A Newman, Ramray Bhat + Show 1 more

Open Access

https://doi.org/10.1016/j.biosystems.2021.104502

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Abstract

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.

Highlights

The mesenchymal tissue of the developing vertebrate limb bud is an excitable medium that sustains both spatial and temporal periodic phenomena
Spatial periodicity is seen in phyla lacking segmented bodies as adults: the tentacles of cnidarian hydra and molluscan octopuses are evenly spaced around the respective mouth regions, and the appendages of echinoderm starfish, often five in number but up to several dozen depending on the species, are uniformly distributed around the central organ-containing region
Each successively forming somite becomes individuated from the unsegmented plate all at once, so their cells must be in the same responsive state just as they

Summary

Introduction: spatial and temporal waves in animal development

The bodies of most animal phyla exhibit spatially periodic structures, which is obvious in segmented forms like arthropods, annelid worms, and vertebrates. Synchronization occurs within tissue blocks on either side of the neural tube, causing prospective somites to respond to morphogenetic signals, i.e., those that induce regionalization or local cell rearrangement, in a concerted fashion Since it does not require transport of materials such as morphogens or ions between or through a tissue, synchrony of cellular oscillators is an efficient way to bring about this coordination, since it acts without attenuation over distances greater than molecular diffusion or facilitated transport. The existence of intermediate germband insects, which exhibit both progressive sequential segmentation in a cellularized portion of the embryo and simultaneous segmentation in a syncytial region suggests that these are variations on the same mechanism (Clark, 2017; Salazar-Ciudad et al, 2001)

Spatial periodicities of the vertebrate limb skeleton

The 2GL system has no temporally oscillating modes

Conclusions