Segment-Specific Adhesion as a Driver of Convergent Extension

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.

会聚延伸（Convergent extension）是胚胎发育过程中形成主体轴的关键事件，指组织同时发生伸长与缩窄的生物学过程。其涉及多尺度的调控过程：涵盖亚细胞、细胞及组织水平，并通过外显或内在反馈机制实现跨尺度相互作用。计算建模研究在解析会聚延伸背后的多尺度反馈机制中发挥着重要作用。

会聚延伸通常发生在已被模式化或正在被模式化为不同基因表达域的组织中。迄今为止，在会聚延伸的大规模组织运动过程中，此类组织模式如何得以维持这一科学问题尚未得到系统研究。有趣的是，实验数据表明，在某些情况下，这些组织模式反而可能驱动会聚延伸，而非仅需抵御会聚延伸以维持自身稳定性。

本研究采用预模式化为节段的组织的二维细胞Potts模型（2D Cellular Potts Model, CPM），实验结果显示：会聚延伸往往会破坏这一预先存在的节段模式。但当细胞优先与同节段类型的细胞发生黏附时，节段完整性得以维持，且组织伸长过程未受到任何抑制。值得注意的是，我们证明了这种节段特异性黏附本身就足以驱动会聚延伸过程。

当我们为模拟体系中的细胞赋予运动持久性时，会聚延伸过程会得到显著增强——而在活体组织中，这种运动持久性自然源自细胞骨架动力学。最后，我们通过拓展模型验证了研究结果的普适性：在仅能沿单一方向延伸的组织（此类情况常因胚胎头部区域的惯性而出现），以及预模式化为一系列域并形成两个相反黏附梯度而非交替节段的组织中，差异黏附对会聚延伸均表现出类似的调控效果。