Multicellular organization by a non-diffusible signal: Mathematical and experimental analysis of morphogenetic cell movements in myxobacteria

发育生物学的基本问题之一是如何从最初均匀的相同细胞群中产生分化细胞（如组织）的空间模式。在这里，一组独特的生物学家，数学家和物理学家解决了这个问题，使用多细胞发育的粘球菌黄质作为一个模型系统。该工作组将采用高度跨学科的方法，将生物实验与定量数学建模和模拟相结合。为了应对饥饿，滑翔细菌M. xanthus的细胞启动了一个多细胞发育程序，导致流动和聚集模式，最终形成充满孢子的子实体。非扩散性c信号在诱导和编排聚集和孢子形成过程中起着关键作用。这一建议的主要目的是建立和分析从单个细胞开始的三维子实体发育的定量数学模型。该数学模型将允许我们研究，细胞表面相关的c信号是否足以解释黏菌的多细胞组织，或者是否需要额外的信号机制（例如，扩散信号机制，它在黏菌Dictyostelium disideum的多细胞组织中起关键作用）。模型预测将在c信号缺失的发育突变体实验中得到验证。该项目有望对生物系统中的模式形成机制提供新的见解，并更好地理解非扩散形态因子如何诱导和组织形态发生细胞运动。

One of the essential problems in developmental biology is how spatial patterns of differentiated cells (e.g. tissues) can arise from an initially uniform mass of identical cells. Here, a unique group of biologists, mathematicians and physicists addresses this question using multicellular development in Myxococcus xanthus as a model system. The working group will apply a highly interdisciplinary approach combining biological experiments with quantitative mathematical modeling and simulation. In response to starvation, cells of the gliding bacterium M. xanthus initiate a multicellular developmental program that leads to streaming and aggregation patterns and culminates in the formation of spore-filled fruiting bodies. The non-diffusible C-signal plays a key role in inducing and choreographing the aggregation and sporulation processes. The main objective of this proposal is the construction and analysis of a quantitative mathematical model for the development of a three-dimensional fruiting body starting from individual cells. The mathematical model will allow us to investigate, whether the cell surface-associated C-signal is sufficient for explaining the multicellular organization of myxobacteria or if additional signaling mechanisms are required (e.g. a diffusive signaling mechanism, which plays a key role in the multicellular organization of the slime mould Dictyostelium discoideum). Model predictions will be validated in experiments with developmental mutants in which C-signaling is deficient. This project promises new insights into pattern formation mechanisms in biological systems and a better understanding of how non-diffusible morphogens may induce and organize morphogenetic cell movements.