O'Dea R D, King J R
Centre for Mathematical Medicine and Biology, School of Mathematical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Math Med Biol. 2013 Jun;30(2):95-113. doi: 10.1093/imammb/dqr028. Epub 2011 Dec 8.
Juxtacrine signalling mechanisms are known to be crucial in tissue and organ development, leading to spatial patterns in gene expression. We investigate the patterning behaviour of a discrete model of juxtacrine cell signalling due to Owen & Sherratt (1998, Mathematical modelling of juxtacrine cell signalling. Math. Biosci., 153, 125-150) in which ligand molecules, unoccupied receptors and bound ligand-receptor complexes are modelled. Feedback between the ligand and receptor production and the level of bound receptors is incorporated. By isolating two parameters associated with the feedback strength and employing numerical simulation, linear stability and bifurcation analysis, the pattern-forming behaviour of the model is analysed under regimes corresponding to lateral inhibition and induction. Linear analysis of this model fails to capture the patterning behaviour exhibited in numerical simulations. Via bifurcation analysis, we show that since the majority of periodic patterns fold subcritically from the homogeneous steady state, a wide variety of stable patterns exists at a given parameter set, providing an explanation for this failure. The dominant pattern is isolated via numerical simulation. Additionally, by sampling patterns of non-integer wavelength on a discrete mesh, we highlight a disparity between the continuous and discrete representations of signalling mechanisms: in the continuous case, patterns of arbitrary wavelength are possible, while sampling such patterns on a discrete mesh leads to longer wavelength harmonics being selected where the wavelength is rational; in the irrational case, the resulting aperiodic patterns exhibit 'local periodicity', being constructed from distorted stable shorter wavelength patterns. This feature is consistent with experimentally observed patterns, which typically display approximate short-range periodicity with defects.
已知旁分泌信号传导机制在组织和器官发育中至关重要,可导致基因表达的空间模式。我们研究了由欧文和谢拉特(1998年,旁分泌细胞信号传导的数学建模。数学生物科学,153,125 - 150)提出的旁分泌细胞信号离散模型的模式形成行为,该模型对配体分子、未占据的受体和结合的配体 - 受体复合物进行了建模。纳入了配体和受体产生与结合受体水平之间的反馈。通过分离与反馈强度相关的两个参数,并采用数值模拟、线性稳定性和分岔分析,在对应于侧向抑制和诱导的情况下分析了模型的模式形成行为。该模型的线性分析未能捕捉数值模拟中表现出的模式形成行为。通过分岔分析,我们表明,由于大多数周期性模式从均匀稳态亚临界折叠,在给定参数集下存在多种稳定模式,这为这种失败提供了解释。通过数值模拟分离出主导模式。此外,通过在离散网格上对非整数波长的模式进行采样,我们突出了信号传导机制的连续和离散表示之间的差异:在连续情况下,任意波长的模式都是可能的,而在离散网格上对这种模式进行采样会导致在波长为有理数时选择更长波长的谐波;在无理数情况下,产生的非周期性模式表现出“局部周期性”,由扭曲的稳定较短波长模式构成。这一特征与实验观察到的模式一致,实验观察到的模式通常显示出带有缺陷的近似短程周期性。