Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
Biomaterials. 2023 Dec;303:122405. doi: 10.1016/j.biomaterials.2023.122405. Epub 2023 Nov 17.
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.
在胚胎发育过程中,组织必须具有精确的物质特性,以确保细胞产生的力导致发育器官的刻板形态。然而,物质特性在发育过程中是如何建立和调节的问题仍未得到充分研究。在这里,我们通过研究肠环形成来解决这些更广泛的问题,肠环形成是一个初始直肠管弯曲成环的过程,允许在体腔内有序排列。环形成是由于管在附着组织(背系膜)的约束下伸长,背系膜被伸长的管弹性拉伸至几乎三倍其长度。这种弹性储能使系膜能够提供稳定的压缩力,最终使管弯曲成环。从系膜的转录组分析开始,我们发现肠环形成过程中细胞外基质相关基因广泛上调,包括与弹性纤维沉积相关的基因。通过分子和力学分析相结合,我们得出结论,弹性蛋白赋予系膜拉伸刚度,使其在组织发育中的作用。这些结果揭示了弹性蛋白作为形态发生驱动因子的作用,超出了其在成人组织中抵抗循环变形的更确定作用。