Mechanics of Development

Abstract

Mechanical forces are integral to development-from the earliest stages of embryogenesis to the construction and differentiation of complex organs. Advances in imaging and biophysical tools have allowed us to delve into the developmental mechanobiology of increasingly complex organs and organisms. Here, we focus on recent work that highlights the diversity and importance of mechanical influences during morphogenesis. Developing tissues experience intrinsic mechanical signals from active forces and changes to tissue mechanical properties as well as extrinsic mechanical signals, including constraint and compression, pressure, and shear forces. Finally, we suggest promising avenues for future work in this rapidly expanding field.

Figure 1.. Intrinsic mechanical forces driving morphogenesis.

(A) During compaction of the 8-cell embryo, tension at the cell-medium interface increases, changing the angles between cells. The increase in tension is accompanied by pulsatile actin dynamics at the cell cortex. (B) Apical actin rings in the 16-cell mouse embryo expand towards intercellular junctions to seal the blastocyst. (C) Hindgut morphogenesis in the chick embryo requires the gut endoderm to fold over onto itself to form the gut tube. This movement is generated by collective cell migration resulting from a gradient of cell contractility that interacts with a stable morphogen gradient to drive tissue flow. (D) Deep cells fluidize at the onset of zebrafish epiboly as they undergo divisions and lose integrity of their cell-cell contacts. As a result, the expanding EVL compresses the deep-cell layer to drive blastoderm thinning.

Figure 2.. Extrinsic mechanical forces driving morphogenesis.

(A) During chick embryogenesis, growth of the intestinal epithelium generates continuous strain to align the first circumferential layer of smooth muscle cells. Subsequently, periodic contractions of the circumferential smooth muscle layer generate cyclic strain to align the outer longitudinal layer of smooth muscle cells. (B) Pressurized microlumens form between cells of the early mouse embryo and, as they combine, break embryonic symmetry and establish a single fluid-filled cavity within the blastocyst. (C) Blood flow drives morphogenesis of the zebrafish heart valve by activating the shear-sensitive transcription factor KLF2 via mechanosensitive ions channels. Downstream flow-responsive signaling through FGF and WNT is required for maintaining the integrity of the myocardial wall and for driving tissue remodelling. Flow also generates patterns of wall shear stress that predict the direction of endocardial cell convergence towards the AVC.