Faculty of Engineering and the Environment, University of Southampton, Highfield Campus, Southampton, SO17 1BJ, UK.
University of Nebraska-Lincoln, 1901 Vine St N231, Lincoln, NE, 68503, USA.
Bull Math Biol. 2019 Apr;81(4):1201-1237. doi: 10.1007/s11538-018-00560-2. Epub 2019 Jan 3.
This paper is concerned with a late stage of lymphangiogenesis in the trunk of the zebrafish embryo. At 48 hours post-fertilisation (HPF), a pool of parachordal lymphangioblasts (PLs) lies in the horizontal myoseptum. Between 48 and 168 HPF, the PLs spread from the horizontal myoseptum to form the thoracic duct, dorsal longitudinal lymphatic vessel, and parachordal lymphatic vessel. This paper deals with the potential of vascular endothelial growth factor C (VEGFC) to guide the differentiation of PLs into the mature lymphatic endothelial cells that form the vessels. We built a mathematical model to describe the biochemical interactions between VEGFC, collagen I, and matrix metalloproteinase 2 (MMP2). We also carried out a linear stability analysis of the model and computer simulations of VEGFC patterning. The results suggest that VEGFC can form Turing patterns due to its relations with MMP2 and collagen I, but the zebrafish embryo needs a separate control mechanism to create the right physiological conditions. Furthermore, this control mechanism must ensure that the VEGFC patterns are useful for lymphangiogenesis: stationary, steep gradients, and reasonably fast forming. Generally, the combination of a patterning species, a matrix protein, and a remodelling species is a new patterning mechanism.
这篇论文研究了斑马鱼胚胎躯干淋巴管生成的晚期阶段。在受精后 48 小时(HPF),一群颅索旁淋巴母细胞(PLs)位于水平肌隔中。在 48 到 168 HPF 之间,PLs 从水平肌隔扩散,形成胸导管、背侧纵行淋巴管和颅索旁淋巴管。本文研究了血管内皮生长因子 C(VEGFC)引导 PL 分化为成熟淋巴管内皮细胞形成血管的潜力。我们构建了一个数学模型来描述 VEGFC、胶原 I 和基质金属蛋白酶 2(MMP2)之间的生化相互作用。我们还对模型进行了线性稳定性分析和 VEGFC 模式的计算机模拟。结果表明,由于 VEGFC 与 MMP2 和胶原 I 的关系,它可以形成图灵模式,但斑马鱼胚胎需要一个单独的控制机制来创造正确的生理条件。此外,该控制机制必须确保 VEGFC 模式对淋巴管生成有用:稳定、陡峭的梯度和合理快速的形成。一般来说,模式物种、基质蛋白和重塑物种的组合是一种新的模式形成机制。