The Francis Crick Institute, London, UK.
Nat Rev Genet. 2021 Jun;22(6):393-411. doi: 10.1038/s41576-021-00342-y. Epub 2021 Mar 25.
Cells within developing tissues rely on morphogens to assess positional information. Passive diffusion is the most parsimonious transport model for long-range morphogen gradient formation but does not, on its own, readily explain scaling, robustness and planar transport. Here, we argue that diffusion is sufficient to ensure robust morphogen gradient formation in a variety of tissues if the interactions between morphogens and their extracellular binders are considered. A current challenge is to assess how the affinity for extracellular binders, as well as other biophysical and cell biological parameters, determines gradient dynamics and shape in a diffusion-based transport system. Technological advances in genome editing, tissue engineering, live imaging and in vivo biophysics are now facilitating measurement of these parameters, paving the way for mathematical modelling and a quantitative understanding of morphogen gradient formation and modulation.
发育组织中的细胞依赖于形态发生素来评估位置信息。对于长距离形态发生梯度的形成，被动扩散是最简约的运输模型，但仅凭自身并不能很好地解释缩放、鲁棒性和平坦运输。在这里，我们认为，如果考虑形态发生素与其细胞外配体之间的相互作用，扩散足以确保在各种组织中形成稳健的形态发生梯度。目前的挑战是评估细胞外配体的亲和力以及其他生物物理和细胞生物学参数如何在基于扩散的运输系统中决定梯度动力学和形状。基因组编辑、组织工程、实时成像和体内生物物理学方面的技术进步现在正在促进这些参数的测量，为形态发生梯度形成和调节的数学建模和定量理解铺平了道路。
