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Morphology changes induced by intercellular gap junction blocking: A reaction-diffusion mechanism
Biosystems ( IF 2.0 ) Pub Date : 2021-08-17 , DOI: 10.1016/j.biosystems.2021.104511
Javier Cervera 1 , Michael Levin 2 , Salvador Mafe 1
Affiliation  

Complex anatomical form is regulated in part by endogenous physiological communication between cells; however, the dynamics by which gap junctional (GJ) states across tissues regulate morphology are still poorly understood. We employed a biophysical modeling approach combining different signaling molecules (morphogens) to qualitatively describe the anteroposterior and lateral morphology changes in model multicellular systems due to intercellular GJ blockade. The model is based on two assumptions for blocking-induced patterning: (i) the local concentrations of two small antagonistic morphogens diffusing through the GJs along the axial direction, together with that of an independent, uncoupled morphogen concentration along an orthogonal direction, constitute the instructive patterns that modulate the morphological outcomes, and (ii) the addition of an external agent partially blocks the intercellular GJs between neighboring cells and modifies thus the establishment of these patterns. As an illustrative example, we study how the different connectivity and morphogen patterns obtained in presence of a GJ blocker can give rise to novel head morphologies in regenerating planaria. We note that the ability of GJs to regulate the permeability of morphogens post-translationally suggests a mechanism by which different anatomies can be produced from the same genome without the modification of gene-regulatory networks. Conceptually, our model biosystem constitutes a reaction-diffusion information processing mechanism that allows reprogramming of biological morphologies through the external manipulation of the intercellular GJs and the resulting changes in instructive biochemical signals.



中文翻译:

细胞间间隙连接阻断诱导的形态变化:一种反应扩散机制

复杂的解剖形式部分受细胞间内源性生理通讯的调节;然而,跨组织的间隙连接(GJ)状态调节形态的动力学仍然知之甚少。我们采用生物物理建模方法结合不同的信号分子(形态发生素)来定性地描述模型多细胞系统中由于细胞间 GJ 阻断引起的前后和横向形态变化。该模型基于阻塞诱导的图案化的两个假设:(i)两个小的拮抗形态发生素的局部浓度沿轴向通过 GJ 扩散,以及一个独立的,沿正交方向的非耦合形态发生素浓度,构成调节形态结果的指导模式,并且(ii)添加外部试剂部分阻断了相邻细胞之间的细胞间 GJ,从而改变了这些模式的建立。作为一个说明性的例子,我们研究了在 GJ 阻滞剂存在下获得的不同连接性和形态发生素模式如何在涡虫再生中产生新的头部形态。我们注意到,GJs 在翻译后调节形态发生素渗透性的能力表明了一种机制,通过这种机制,可以从同一基因组产生不同的解剖结构,而无需修改基因调节网络。从概念上讲,

更新日期:2021-08-19
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