Kavli Institute for Theoretical Physics, University of California, Santa Barbara, Santa Barbara, United States.
Department of Physics, University of California, Santa Barbara, Santa Barbara, United States.
Elife. 2022 May 20;11:e77355. doi: 10.7554/eLife.77355.
Organ architecture is often composed of multiple laminar tissues arranged in concentric layers. During morphogenesis, the initial geometry of visceral organs undergoes a sequence of folding, adopting a complex shape that is vital for function. Genetic signals are known to impact form, yet the dynamic and mechanical interplay of tissue layers giving rise to organs' complex shapes remains elusive. Here, we trace the dynamics and mechanical interactions of a developing visceral organ across tissue layers, from subcellular to organ scale in vivo. Combining deep tissue light-sheet microscopy for in toto live visualization with a novel computational framework for multilayer analysis of evolving complex shapes, we find a dynamic mechanism for organ folding using the embryonic midgut of as a model visceral organ. Hox genes, known regulators of organ shape, control the emergence of high-frequency calcium pulses. Spatiotemporally patterned calcium pulses trigger muscle contractions via myosin light chain kinase. Muscle contractions, in turn, induce cell shape change in the adjacent tissue layer. This cell shape change collectively drives a convergent extension pattern. Through tissue incompressibility and initial organ geometry, this in-plane shape change is linked to out-of-plane organ folding. Our analysis follows tissue dynamics during organ shape change in vivo, tracing organ-scale folding to a high-frequency molecular mechanism. These findings offer a mechanical route for gene expression to induce organ shape change: genetic patterning in one layer triggers a physical process in the adjacent layer - revealing post-translational mechanisms that govern shape change.
器官结构通常由多个层状组织排列成同心层组成。在形态发生过程中,内脏器官的初始几何形状经历了一系列折叠,采用了对功能至关重要的复杂形状。遗传信号已知会影响形态,但导致器官复杂形状的组织层的动态和力学相互作用仍然难以捉摸。在这里,我们在体内从亚细胞到器官尺度上追踪了一个正在发育的内脏器官的动态和组织层之间的力学相互作用。我们结合深层组织光片显微镜进行全活体可视化和用于分析不断变化的复杂形状的多层计算框架,以胚胎中肠作为内脏器官模型,发现了一种器官折叠的动态机制。Hox 基因是已知的器官形状调节剂,控制高频钙脉冲的出现。时空模式化的钙脉冲通过肌球蛋白轻链激酶触发肌肉收缩。肌肉收缩反过来诱导相邻组织层中的细胞形状变化。这种细胞形状变化共同驱动收敛扩展模式。通过组织不可压缩性和初始器官几何形状,这种面内形状变化与器官的面外折叠有关。我们的分析跟踪了体内器官形状变化过程中的组织动力学,将器官级别的折叠追踪到高频分子机制。这些发现为基因表达诱导器官形状变化提供了一种机械途径:一层的遗传模式触发相邻层的物理过程——揭示了控制形状变化的翻译后机制。