How diverse cell fates and complex forms emerge and feed back to each other to sculpt functional organs remains unclear. In the developing heart, the myocardium transitions from a simple epithelium to an intricate tissue that consists of distinct layers: the outer compact and inner trabecular layers. Defects in this process, which is known as cardiac trabeculation, cause cardiomyopathies and embryonic lethality, yet how tissue symmetry is broken to specify trabecular cardiomyocytes is unknown. Here we show that local tension heterogeneity drives organ-scale patterning and cell-fate decisions during cardiac trabeculation in zebrafish. Proliferation-induced cellular crowding at the tissue scale triggers tension heterogeneity among cardiomyocytes of the compact layer and drives those with higher contractility to delaminate and seed the trabecular layer. Experimentally, increasing crowding within the compact layer cardiomyocytes augments delamination, whereas decreasing it abrogates delamination. Using genetic mosaics in trabeculation-deficient zebrafish models-that is, in the absence of critical upstream signals such as Nrg-Erbb2 or blood flow-we find that inducing actomyosin contractility rescues cardiomyocyte delamination and is sufficient to drive cardiomyocyte fate specification, as assessed by Notch reporter expression in compact layer cardiomyocytes. Furthermore, Notch signalling perturbs the actomyosin machinery in cardiomyocytes to restrict excessive delamination, thereby preserving the architecture of the myocardial wall. Thus, tissue-scale forces converge on local cellular mechanics to generate complex forms and modulate cell-fate choices, and these multiscale regulatory interactions ensure robust self-organized organ patterning.

中文翻译：

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张力异质性指导形式和命运塑造心肌壁

不同的细胞命运和复杂的形式如何出现并相互反馈以塑造功能器官仍不清楚。在发育中的心脏中，心肌从简单的上皮细胞转变为由不同层组成的复杂组织：外部致密层和内部小梁层。这个过程中的缺陷（称为心脏小梁形成）会导致心肌病和胚胎致死，但如何破坏组织对称性以指定小梁心肌细胞尚不清楚。在这里，我们表明局部张力异质性驱动斑马鱼心脏小梁形成过程中的器官尺度模式和细胞命运决定。组织尺度上增殖诱导的细胞拥挤触发致密层心肌细胞之间的张力异质性，并驱使具有较高收缩性的细胞分层和播种小梁层。实验上，增加致密层心肌细胞内的拥挤会增加分层，而减少它会消除分层。在缺乏小梁的斑马鱼模型中使用遗传马赛克 - 也就是说，在没有关键上游信号（如 Nrg-Erbb2 或血流）的情况下，我们发现诱导肌动球蛋白收缩性可以挽救心肌细胞分层，并足以驱动心肌细胞命运规范，如评估Notch 报告基因在致密层心肌细胞中的表达。此外，Notch 信号会扰乱心肌细胞中的肌动球蛋白机制以限制过度分层，从而保留心肌壁的结构。因此，组织尺度的力量会聚在局部细胞力学上以产生复杂的形式并调节细胞命运的选择，这些多尺度的调节相互作用确保了强大的自组织器官模式。