Spatial waves and temporal oscillations in vertebrate limb development

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.

发育中的脊椎动物肢芽的间充质组织是一种可兴奋介质，它能维持时空周期性现象。首先是一般图灵型反应 - 扩散动力学的结果，这种动力学产生细胞凝聚的空间驻波。这些凝聚物转变为软骨的结节和杆状结构，并最终（在大多数物种中）成为骨性内骨骼。其次，时间周期性源于细胞内调节动力学，这种动力学使一种或多种基因的表达产生振荡，其产物调节空间模式形成系统。在此，我们回顾来自鸡胚的实验证据，通过一组数学和计算模型解释，空间波形成系统基于两种聚糖结合蛋白，即半乳糖凝集素 - 1A和半乳糖凝集素 - 8，它们相互作用以及与产生它们的细胞相互作用，并且时间振荡发生在转录辅调节因子Hes1的表达中。Hes1振荡在肢芽中的多细胞同步作用是在整体上协调间充质细胞的生化状态，从而细化和锐化空间模式。重要的是，与大多数图灵型系统不同，基于反应 - 扩散的波形成机制本身不包含振荡核心，并且可能随着它纳入使能其模式形成能力的细胞 - 基质黏附模块而进化到这种状态。