Mechanical control of tissue shape: Cell-extrinsic and -intrinsic mechanisms join forces to regulate morphogenesis

Abstract

During vertebrate development, cells must proliferate, move, and differentiate to form complex shapes. Elucidating the mechanisms underlying the molecular and cellular processes involved in tissue morphogenesis is essential to understanding developmental programmes. Mechanical stimuli act as a major contributor of morphogenetic processes and impact on cell behaviours to regulate tissue shape and size. Specifically, cell extrinsic physical forces are translated into biochemical signals within cells, through the process of mechanotransduction, activating multiple mechanosensitive pathways and defining cell behaviours. Physical forces generated by tissue mechanics and the extracellular matrix are crucial to orchestrate tissue patterning and cell fate specification. At the cell scale, the actomyosin network generates the cellular tension behind the tissue mechanics involved in building tissue. Thus, understanding the role of physical forces during morphogenetic processes requires the consideration of the contribution of cell intrinsic and cell extrinsic influences. The recent development of multidisciplinary approaches, as well as major advances in genetics, microscopy, and force-probing tools, have been key to push this field forward. With this review, we aim to discuss recent work on how tissue shape can be controlled by mechanical forces by focusing specifically on vertebrate organogenesis. We consider the influences of mechanical forces by discussing the cell-intrinsic forces (such as cell tension and proliferation) and cell-extrinsic forces (such as substrate stiffness and flow forces). We review recently described processes supporting the role of intratissue force generation and propagation in the context of shape emergence. Lastly, we discuss the emerging role of tissue-scale changes in tissue material properties, extrinsic forces, and shear stress on shape establishment.

Keywords: Mechanical forces; Mechanotransduction; Morphogenesis; Tissue shape; Vertebrate development; Vertebrate organogenesis.