The physical properties behind an embryo’s body plan

Gastrulation is the stage in embryonic development when the first 'morphogenetic' changes happen: the embryo turns from a hollow ball of cells into a multilayered structure. At the same time, the different germ layers that define the body plan are being specified. 

Renowned developmental biologist Lewis Wolpert once asserted: “It's not birth, marriage or death, but gastrulation which is truly the most important time of your life,” and head of the Crick’s Mathematical and Physical Biology Laboratory, Zena Hadjivasiliou, agrees. “This is a hugely important period of development, where the embryo is under lots of competing pressures all at once,” she explains. “It needs to grow and change its shape but also make sure everything happens in the right place, and quickly, otherwise errors can be fatal." 

Zena Hadjivasiliou.

This period has been of interest for developmental biologists for a long time, as they try to understand how two crucial processes are coordinated: tissues changing shape, and cells within them acquiring different fates.

Zena's collaborator, Nicoletta Petridou, a group leader at EMBL, had been studying the role of changes in cell connectivity prior to gastrulation in zebrafish embryos, finding that just before gastrulation, the tissue becomes more connected. Where it's more connected, it's more rigid.

Embryos and developing tissues need to change their material properties to be able to reshape themselves. "It's kind of like glass being heated up so that it can mould and change into a new shape," describes Zena. "The changing state from soft to rigid and back is akin to this process, allowing the embryo to be moulded."

Zena's lab is interested in how tissue architecture and material properties affect the dispersion of chemical signals called morphogens, which instruct cells what to become and when. Her team bring a theoretical perspective to developmental biology, which perfectly complements Nicoletta's work.

Regulating patterning 

In a recent collaborative study, published in Nature Cell Biology, the researchers used a mixture of theoretical modelling and computer simulations to predict how morphogens are likely to be affected by tissue material properties, like rigidity. They combined this with experiments to understand how rapid changes in tissue rigidity are coordinated with biochemical processes. 

"We showed that tissue rigidity and cell patterning are both regulated by the same morphogen," Zena explains. “On further exploration, we also found that the morphogen, called Nodal, can't diffuse as far into the tissue where it becomes more rigid, because the tissue becomes more porous.”

This is a smart feedback loop, where Nodal makes the tissue become more rigid, which in turn stops Nodal from diffusing too far and switches off patterning in this area. 

"We also found that Nodal’s limited ability to diffuse means concentration of the morphogen builds up near the tissue edge and it promptly activates its own inhibitor, Lefty," Zena adds. "This means developmental cell signalling is intrinsically linked to structural changes at the tissue level, and this ensures that the correct amount of a certain cells are made.”

Zena believes this closed two-way feedback loop is a way of tissues maintaining robustness against changing environments. The multidisciplinary team now want to explore whether this process also occurs in other animal or human embryos, and what happens when coordination fails.

“Tissue material properties do more than enable mechanical deformation – they actively influence biological information,” says Nicoletta, who also led on a companion study in Nature Physics to dive deeper into how the physical properties of rigidity trigger embryonic organisation. “Tissue material states and their transitions are deeply integrated within developmental biology, with continuous crosstalk between physical and biochemical processes.”