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ROBUSTNESS OF MORPHOGEN GRADIENTS WITH BUCKET BRIGADE TRANSPORT THROUGH MEMBRANE-ASSOCIATED NON-RECEPTORS

机译:形态发生素梯度分布具有鲁棒性桶式输运膜相关的非受体

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摘要

Robust multiple-fate morphogen gradients are essential for embryo development. Here, we analyze mathematically a model of morphogen gradient (such as Dpp in Drosophila wing imaginal disc) formation in the presence of non-receptors with both diffusion of free morphogens and the movement of morphogens bound to non-receptors. Under the assumption of rapid degradation of unbound morphogen, we introduce a method of functional boundary value problem and prove the existence, uniqueness and linear stability of a biologically acceptable steady-state solution. Next, we investigate the robustness of this steady-state solution with respect to significant changes in the morphogen synthesis rate. We prove that the model is able to produce robust biological morphogen gradients when production and degradation rates of morphogens are large enough and non-receptors are abundant. Our results provide mathematical and biological insight to a mechanism of achieving stable robust long distance morphogen gradients. Key elements of this mechanism are rapid turnover of morphogen to non-receptors of neighoring cells resulting in significant degradation and transport of non-receptor-morphogen complexes, the latter moving downstream through a “bucket brigade” process.
机译:强大的多重命运形态发生子梯度对于胚胎发育至关重要。在这里,我们在数学上分析了在存在非受体的情况下形成形态发生剂梯度的模型(例如,果蝇翅膀假想盘中的Dpp),其中游离形态发生剂的扩散和与非受体结合的形态发生剂的运动都存在。在未结合的形态发生子快速降解的假设下,我们引入了一种函数边值问题的方法,并证明了生物学上可接受的稳态溶液的存在性,唯一性和线性稳定性。接下来,我们研究该稳态溶液相对于形态发生子合成速率的显着变化的鲁棒性。我们证明,当形态发生子的产生和降解速率足够大且非受体丰富时,该模型能够产生健壮的生物形态发生梯度。我们的结果为实现稳定的长距离长途形态发生剂梯度的机理提供了数学和生物学见解。该机制的关键要素是吗啡生成素快速转移到邻近细胞的非受体上,从而导致非受体-吗啡基复合物的显着降解和转运,后者通过“水桶旅”过程向下游移动。

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