PDF(Pubmed)
Abstract：
During embryonic development, tissues must possess precise material properties to ensure that cell-generated forces give rise to the stereotyped morphologies of developing organs. However, the question of how material properties are established and regulated during development remains understudied. Here, we aim to address these broader questions through the study of intestinal looping, a process by which the initially straight intestinal tube buckles into loops, permitting ordered packing within the body cavity. Looping results from elongation of the tube against the constraint of an attached tissue, the dorsal mesentery, which is elastically stretched by the elongating tube to nearly triple its length. This elastic energy storage allows the mesentery to provide stable compressive forces that ultimately buckle the tube into loops. Beginning with a transcriptomic analysis of the mesentery, we identified widespread upregulation of extracellular matrix related genes during looping, including genes related to elastic fiber deposition. Combining molecular and mechanical analyses, we conclude that elastin confers tensile stiffness to the mesentery, enabling its mechanical role in organizing the developing small intestine. These results shed light on the role of elastin as a driver of morphogenesis that extends beyond its more established role in resisting cyclic deformation in adult tissues.
摘要：
在胚胎发育过程中,组织必须具有精确的材料特性，以确保细胞产生的力引起发育器官的定型形态。然而,在开发过程中如何建立和调节材料特性的问题仍未得到充分研究。这里,我们的目标是通过肠道循环的研究来解决这些更广泛的问题，最初笔直的肠管弯曲成环的过程，允许在体腔内订购包装。循环是由于管相对于附着组织的约束而伸长的结果，背侧肠系膜,它被伸长的管子弹性拉伸到其长度的三倍。这种弹性能量储存允许肠系膜提供最终使管弯曲成环的稳定压缩力。从肠系膜的转录组学分析开始，我们发现在循环过程中细胞外基质相关基因的广泛上调，包括与弹性纤维沉积相关的基因。结合分子和机械分析，我们得出结论，弹性蛋白赋予肠系膜拉伸刚度，使其在组织发育中的小肠中发挥机械作用。这些结果阐明了弹性蛋白作为形态发生驱动器的作用，该作用超出了其在抵抗成体组织周期性变形中的更确定作用。
