Relieving the Pressure on Tissue Development.
Relieving the Pressure on Tissue Development.
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减轻组织发育的压力。
DOI：
10.1016/j.bpj.2017.06.006
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发表时间：
2017
影响因子：
3.4
通讯作者：
Kinzer-Ursem,Tamara
中科院分区：
文献类型：
--
作者：
Kinzer-Ursem,Tamara
了解胚胎发育过程中组织模式是如何出现的，是发育生物学的长期目标。特别是，导致细胞分化并最终导致成人组织的细胞外和细胞内机械力和生化线索之间的复杂相互作用仍然是一个活跃的研究领域。主要的挑战之一是，允许同时测量机械力和生化信号的实验方法有限。在这一期的《生物物理学杂志》中，Narciso等人(1)在他们描述的一种微型分析设备方面取得了令人兴奋的实验进展，该设备可以在发育中的果蝇器官的直接环境中对外部机械应力进行严格控制，同时允许对细胞内生化信号信号进行成像。常见的果蝇黑腹果蝇长期以来一直是发育生物学的模式生物。对果蝇翅膀形象盘发育的研究有助于我们目前对形态原梯度及其相关的遗传和生化调节网络如何在发育中的组织中促进细胞分化和图案形成的理解。社区资源，如FlyBase。Org允许研究人员快速搜索已测序的基因组，识别突变菌株，执行基因本体论分析，并访问RNAseq、RNA干扰和CRISPR实施的工具(2)。事实上，转基因菌株的可获得性(有超过22,000个可用)，结合CRISPR和RNA干扰，允许快速筛选促成细胞和组织水平行为的基因和生化途径(3)。这些实验工具，结合形态梯度的计算模型(4)(在(5)中回顾)，极大地促进了我们目前对胚胎发育的理解。除了遗传和生化调控网络，机械信号已经成为细胞行为的重要基本调控因素。细胞产生和响应机械提示的能力对于适当的形态发生和组织模式至关重要(在(6)中回顾)。最近的工作已经开始在各种模型系统中将机械应激与生化信号联系起来。例如，光遗传和荧光生物传感器与机械驱动和力场产生的组合已经开始能够实时操纵细胞信号(在(7)中回顾)。利用高速视频和颗粒跟踪分析实现的微观流变学，在果蝇早期胚胎中测量了细胞内力[8]。此外，细胞间钙波(ICW)通过组织传播，在创伤模型(9)中与放线肌球蛋白细胞骨架的快速重排有关，在果蝇想象翼盘(10，11)中与整个组织对机械应力的反应有关。在最近这项工作的基础上，Narciso等人(1)概述了一种新的微量分析设备和相应的方法，用于定量研究细胞外机械力和生化信号之间的联系。这项工作代表了在控制和量化施加在组织上的外部压力的能力方面的重大技术进步。该设备允许同时进行相关生物组织的活细胞/器官型培养，可以对培养中的翼盘(或潜在的其他器官型制剂)提供受控制的机械压缩，并允许对细胞/组织中由此产生的变化(例如，位移、钙波传播和生长)进行定量测量。此外，该设备还支持…
Understanding how tissue patterning emerges during embryogenesis is a long-standing goal of developmental biology. In particular, the complex interplay between extracellular and intracellular mechanical forces and biochemical cues that lead to cellular differentiation and ultimately adult tissue remains an active area of investigation. One of the main challenges has been that experimental methods that allow for the simultaneous measurement of mechanical force and biochemical signaling are limited. In this issue of Biophysical Journal, Narciso et al.(1) present an exciting experimental advance in their description of a microanalysis device that provides tight control of external mechanical stress in the immediate environment of a developing Drosophila organ while simultaneously allowing for imaging of intracellular biochemical signaling cues. The common fruit fly Drosophila melanogaster has long been a model organism in developmental biology. Studies on development of the Drosophila wing imaginal disk have greatly contributed to our current understanding of how morphogen gradients and their associated genetic and biochemical regulatory networks contribute to cellular differentiation and pattern formation in developing tissues. Community resources such as FlyBase. org allow researchers to rapidly search sequenced genomes, identify mutant strains, perform gene ontology analysis, and access tools for RNaseq, RNA interference, and CRISPR implementation (2). Indeed, the availability of transgenic strains (over 22,000 are available), combined with CRISPR and RNA interference, allows for rapid screening of genes and biochemical pathways that contribute to cellular and tissue-level behaviors (3). These experimental tools, in combination with computational modeling of morphogen gradients (4)(reviewed in (5)), have greatly contributed to our current understanding of embryo development. In addition to genetic and biochemical regulatory networks, mechanical cues have emerged as important fundamental regulators of cellular behavior. The ability of cells to both generate and respond to mechanical cues is critical for proper morphogenesis and tissue patterning (reviewed in (6)). Recent work has started to link mechanical stress with biochemical signaling in various model systems. For example, the combination of optogenetic and fluorescent biosensors with mechanical actuation and force-field generation has started to enable manipulation of cell signaling in real time (reviewed in (7)). Intracellular forces have been measured in early Drosophila embryos using microrheology enabled by high-speed video and particle tracking analysis (8). Moreover, intercellular Ca2+ waves (ICWs) propagating through tissues have been implicated in rapid actinomyosin cytoskeletal rearrangement in wounding models (9) and in tissuewide responses to mechanical stress in vivo in the Drosophila imaginal wing disk (10, 11). Building on this recent work, Narciso et al.(1) outline a new microanalytical device and corresponding methods for quantitatively studying the connections between extracellular mechanical forces and biochemical signaling. This work represents a significant technical advance in the ability to control and quantify the external pressure forces applied to a tissue. The device allows for simultaneous live cell/organotypic culture of relevant biological tissues, can deliver regulated mechanical compression to wing discs (or potentially other organotypic preparations) in culture, and allows for quantitative measurement of the resultant changes in the cells/tissues (eg, displacement, Ca2+ wave propagation, and growth). Furthermore, the device …