Vroomans Renske M A, Hogeweg Paulien, ten Tusscher Kirsten H W J
Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands.
PLoS Comput Biol. 2015 Feb 23;11(2):e1004092. doi: 10.1371/journal.pcbi.1004092. eCollection 2015 Feb.
Convergent extension, the simultaneous extension and narrowing of tissues, is a crucial event in the formation of the main body axis during embryonic development. It involves processes on multiple scales: the sub-cellular, cellular and tissue level, which interact via explicit or intrinsic feedback mechanisms. Computational modelling studies play an important role in unravelling the multiscale feedbacks underlying convergent extension. Convergent extension usually operates in tissue which has been patterned or is currently being patterned into distinct domains of gene expression. How such tissue patterns are maintained during the large scale tissue movements of convergent extension has thus far not been investigated. Intriguingly, experimental data indicate that in certain cases these tissue patterns may drive convergent extension rather than requiring safeguarding against convergent extension. Here we use a 2D Cellular Potts Model (CPM) of a tissue prepatterned into segments, to show that convergent extension tends to disrupt this pre-existing segmental pattern. However, when cells preferentially adhere to cells of the same segment type, segment integrity is maintained without any reduction in tissue extension. Strikingly, we demonstrate that this segment-specific adhesion is by itself sufficient to drive convergent extension. Convergent extension is enhanced when we endow our in silico cells with persistence of motion, which in vivo would naturally follow from cytoskeletal dynamics. Finally, we extend our model to confirm the generality of our results. We demonstrate a similar effect of differential adhesion on convergent extension in tissues that can only extend in a single direction (as often occurs due to the inertia of the head region of the embryo), and in tissues prepatterned into a sequence of domains resulting in two opposing adhesive gradients, rather than alternating segments.
汇聚延伸,即组织同时进行延伸和变窄,是胚胎发育过程中主体轴形成的关键事件。它涉及多个尺度的过程:亚细胞、细胞和组织水平,这些过程通过明确的或内在的反馈机制相互作用。计算建模研究在揭示汇聚延伸背后的多尺度反馈方面发挥着重要作用。汇聚延伸通常在已形成图案或正在形成不同基因表达域图案的组织中起作用。到目前为止,尚未研究在汇聚延伸的大规模组织运动过程中这种组织图案是如何维持的。有趣的是,实验数据表明,在某些情况下,这些组织图案可能驱动汇聚延伸,而不是需要防止汇聚延伸。在这里,我们使用一个二维细胞Potts模型(CPM),该模型将组织预先图案化为节段,以表明汇聚延伸往往会破坏这种预先存在的节段图案。然而,当细胞优先与相同节段类型的细胞粘附时,节段完整性得以维持,而组织延伸没有任何减少。引人注目的是,我们证明这种节段特异性粘附本身就足以驱动汇聚延伸。当我们赋予计算机模拟细胞运动持续性时,汇聚延伸会增强,在体内这自然会由细胞骨架动力学导致。最后,我们扩展模型以确认我们结果的普遍性。我们在只能沿单一方向延伸的组织(如由于胚胎头部区域的惯性经常发生的情况)以及预先图案化为一系列域从而产生两个相反粘附梯度而非交替节段的组织中,证明了差异粘附对汇聚延伸具有类似的影响。