Höfer T, Sherratt J A, Maini P K
Centre for Mathematical Biology, University of Oxford, U.K.
Proc Biol Sci. 1995 Mar 22;259(1356):249-57. doi: 10.1098/rspb.1995.0037.
The dynamics which govern the establishment of pattern and form in multicellular organisms remain a key problem of developmental biology. We study this question in the case of morphogenesis during aggregation of the slime mould Dictyostelium discoideum. Here detailed experimental information allows the formulation of a mechanistic model in which the central element is the coupling of the previously much-studied intracellular cyclic AMP signalling with the chemotactic cell response in cyclic AMP gradients. Numerical simulations of the model show quantitatively how signal relay, chemotactic movement and adaptation orchestrate the collective modes of cell signalling and migration in the aggregating cell layer. The interaction of chemotaxis with the cyclic AMP excitation waves causes the initially homogeneous cell layer to become unstable towards the formation of a branching cell stream pattern with close cell-cell contacts as observed in situ. The evolving cell morphology in turn leads to a pattern of non-homogeneous excitability of the medium and thus feeds back into the cAMP dynamics. This feedback can explain the decrease in signalling period and propagation speed with time, as well as observations on the structure of the spiral wave core in this self-organized excitable medium.
在多细胞生物体中，控制模式和形态形成的动力学仍然是发育生物学的一个关键问题。我们以黏菌盘基网柄菌聚集过程中的形态发生为例来研究这个问题。在这里，详细的实验信息使得构建一个机械模型成为可能，该模型的核心要素是将之前被广泛研究的细胞内环状AMP信号传导与环状AMP梯度中的趋化细胞反应相耦合。该模型的数值模拟定量地展示了信号传递、趋化运动和适应性如何在聚集细胞层中协调细胞信号传导和迁移的集体模式。趋化作用与环状AMP激发波的相互作用使得最初均匀的细胞层朝着形成具有紧密细胞间接触的分支细胞流模式发展，这与原位观察结果一致。不断演变的细胞形态反过来又导致介质兴奋性的不均匀模式，从而反馈到cAMP动力学中。这种反馈可以解释信号周期和传播速度随时间的降低，以及对这种自组织可兴奋介质中螺旋波核心结构的观察结果。
