Marée A F, Hogeweg P
Theoretical Biology and Bioinformatics, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3879-83. doi: 10.1073/pnas.061535198.
When individual amoebae of the cellular slime mold Dictyostelium discoideum are starving, they aggregate to form a multicellular migrating slug, which moves toward a region suitable for culmination. The culmination of the morphogenesis involves complex cell movements that transform a mound of cells into a globule of spores on a slender stalk. The movement has been likened to a "reverse fountain," whereby prestalk cells in the upper part form a stalk that moves downwards and anchors to the substratum, while prespore cells in the lower part move upwards to form the spore head. So far, however, no satisfactory explanation has been produced for this process. Using a computer simulation that we developed, we now demonstrate that the processes that are essential during the earlier stages of the morphogenesis are in fact sufficient to produce the dynamics of the culmination stage. These processes are cAMP signaling, differential adhesion, cell differentiation, and production of extracellular matrix. Our model clarifies the processes that generate the observed cell movements. More specifically, we show that periodic upward movements, caused by chemotactic motion, are essential for successful culmination, because the pressure waves they induce squeeze the stalk downwards through the cell mass. The mechanisms revealed by our model have a number of self-organizing and self-correcting properties and can account for many previously unconnected and unexplained experimental observations.
当细胞黏菌盘基网柄菌的单个变形虫处于饥饿状态时,它们会聚集形成一个多细胞移动蛞蝓体,该蛞蝓体朝着适合最终发育的区域移动。形态发生的最终阶段涉及复杂的细胞运动,这些运动将一堆细胞转化为细长茎上的一团孢子。这种运动被比作“反向喷泉”,即上部的前柄细胞形成向下移动并锚定在基质上的茎,而下部的前孢子细胞向上移动形成孢子头。然而,到目前为止,对于这个过程还没有令人满意的解释。通过我们开发的计算机模拟,我们现在证明,在形态发生早期阶段必不可少的过程实际上足以产生最终阶段的动态变化。这些过程包括环磷酸腺苷(cAMP)信号传导、差异黏附、细胞分化和细胞外基质的产生。我们的模型阐明了产生观察到的细胞运动的过程。更具体地说,我们表明,由趋化运动引起的周期性向上运动对于成功的最终发育至关重要,因为它们诱导的压力波通过细胞团将茎向下挤压。我们的模型揭示的机制具有许多自组织和自我纠正特性,并且可以解释许多以前未关联和未解释的实验观察结果。