Mechanical Forces Reshape Differentiation Cues That Guide Cardiomyogenesis.
Mechanical Forces Reshape Differentiation Cues That Guide Cardiomyogenesis.
复制标题
DOI：
10.1161/circresaha.115.305139
复制
发表时间：
2016-01-22
影响因子：
20.1
通讯作者：
Engler AJ
中科院分区：
文献类型：
--
作者：
Happe CL;Engler AJ
可溶性形态发生梯度在心脏特化和模式化的背景下已经研究了很长时间。然而，最近的数据开始挑战长期体内观察仅由这些梯度驱动的概念。从干细胞到离体生物物理测定的多种生物模型的证据现在支持机械力不仅在调节细胞行为中而且在称为机械转导的过程中从头诱导细胞行为的作用。连接细胞与其生态位的结构蛋白，例如整合素和钙粘蛋白，以及直接或间接与其他生长因子受体偶联的结构蛋白，似乎介导了这些变化，尽管具体的机制细节仍在阐明中。本文综述了无翅（Wnt）、转化生长因子-β和骨形态发生蛋白信号通路对心肌发生的影响，并重点介绍了各通路与机械力之间的相互作用。此外，我们将概述整合素和钙粘蛋白在心脏发育过程中的作用。对于每一个，我们将描述相互作用如何改变心肌形成过程中的多个过程，包括未分化细胞的特化，建立心脏模式以完成管和腔室的形成，或在完全形成的心脏中肌细胞的成熟。
Soluble morphogen gradients have long been studied in the context of heart specification and patterning. However, recent data have begun to challenge the notion that long-standing in vivo observations are driven solely by these gradients alone. Evidence from multiple biological models, from stem cells to ex vivo biophysical assays, now supports a role for mechanical forces in not only modulating cell behavior but also inducing it de novo in a process termed mechanotransduction. Structural proteins that connect the cell to its niche, for example, integrins and cadherins, and that couple to other growth factor receptors, either directly or indirectly, seem to mediate these changes, although specific mechanistic details are still being elucidated. In this review, we summarize how the wingless (Wnt), transforming growth factor-β, and bone morphogenetic protein signaling pathways affect cardiomyogenesis and then highlight the interplay between each pathway and mechanical forces. In addition, we will outline the role of integrins and cadherins during cardiac development. For each, we will describe how the interplay could change multiple processes during cardiomyogenesis, including the specification of undifferentiated cells, the establishment of heart patterns to accomplish tube and chamber formation, or the maturation of myocytes in the fully formed heart.