Force production and mechanical accommodation during convergent extension

Abstract

Forces generated within the embryo during convergent extension (CE) must overcome mechanical resistance to push the head away from the rear. As mechanical resistance increases more than eightfold during CE and can vary twofold from individual to individual, we have proposed that developmental programs must include mechanical accommodation in order to maintain robust morphogenesis. To test this idea and investigate the processes that generate forces within early embryos, we developed a novel gel-based sensor to report force production as a tissue changes shape; we find that the mean stress produced by CE is 5.0±1.6 Pascal (Pa). Experiments with the gel-based force sensor resulted in three findings.(1) Force production and mechanical resistance can be coupled through myosin contractility. The coupling of these processes can be hidden unless affected tissues are challenged by physical constraints. (2) CE is mechanically adaptive; dorsal tissues can increase force production up to threefold to overcome a stiffer microenvironment. These findings demonstrate that mechanical accommodation can ensure robust morphogenetic movements against environmental and genetic variation that might otherwise perturb development and growth. (3) Force production is distributed between neural and mesodermal tissues in the dorsal isolate, and the notochord, a central structure involved in patterning vertebrate morphogenesis, is not required for force production during late gastrulation and early neurulation. Our findings suggest that genetic factors that coordinately alter force production and mechanical resistance are common during morphogenesis, and that their cryptic roles can be revealed when tissues are challenged by controlled biophysical constraints.

Measuring forces and stressesin situin living tissues

“…Alternatively, gel sensors can be external instead of internal to yield accurate tissue-scale force determinations. For example, embedding Xenopus embryo tissue in soft agarose gels of differing stiffness has shown that dorsal tissues undergoing convergent extension upregulate force production when embedded in a stiffer microenvironment (Zhou et al, 2015).…”

Molecular model for force production and transmission during vertebrate gastrulation

“…These protrusions attach to and apply tractional forces to neighboring cells as the cell shortens, pulling cells between one another in support of intercalation. As the cells wedge between one another they generate an extension force of between 0.6 and 5 μN as measured in smaller dorsal tissue isolates or larger whole axial/paraxial explants, respectively (Moore, 1994;Moore et al, 1995;Zhou et al, 2015). The forces generated during Xenopus CE are tissue autonomous and internally generated (Keller and Danilchik, 1988).…”

Mechanical Forces Reshape Differentiation Cues That Guide Cardiomyogenesis

“…Whether examined in vitro or in vivo, these cues come in many forms; generally they can be categorized as passive stimuli that occur within the microenvironment surrounding each lineage 7–9 or as active forces that are directly applied to cells by other cells or fluids. 10–13 For the former case, cells must directly probe the environment through myosin-mediated contractions to sense changes in their surroundings and use the mechanical feedback it provides to elicit changes in cell behavior. 14,15 Conversely the latter case requires the cell to remodel internally or migrate to transmit the load, 16 a process that could activate similar molecular mechanisms.…”

“…14,15 Conversely the latter case requires the cell to remodel internally or migrate to transmit the load, 16 a process that could activate similar molecular mechanisms. 15 Regardless of their type and mechanism, these cues can be studied in model organisms 10 or built into protocols to direct stem cell specification or to test their influence more generally as a cue on cell behavior. 17 Although significant evidence from developmental biology exists on soluble gradients, there is growing evidence using unique physical assays ex vivo and engineered microenvironments in vitro that mechanical cues and their interplay with chemical signals influence specification, which we will focus on here.…”