Chemical and mechanical pattern formation is fundamental during embryogenesis and tissue development. Yet, the underlying molecular and cellular mechanisms are still elusive in many cases. Most current theories assume that tissue development is driven by chemical processes: either as a sequence of chemical patterns each depending on the previous one, or by patterns spontaneously arising from specific chemical interactions (such as “Turing-patterns”). Within both theories, mechanical patterns are usually regarded as passive by-products of chemical pre-patters. However, several experiments question these theories, and an increasing number of studies shows that tissue mechanics can actively influence chemical patterns during development. In this study, we thus focus on the interplay between chemical and mechanical processes during tissue development. On one hand, based on recent experimental data, we develop new mechanochemical simulation models of evolving tissues, in which the full 3D representation of the tissue appears to be critical for obtaining a realistic mechanochemical behaviour. The presented modelling approach is flexible and numerically studied using state of the art finite element methods. Thus, it may serve as a basis to combine simulations with new experimental methods in tissue development. On the other hand, we apply the developed approach and demonstrate that even simple interactions between tissue mechanics and chemistry spontaneously lead to robust and complex mechanochemical patterns. Especially, we demonstrate that the main contradictions arising in the framework of purely chemical theories are naturally and automatically resolved using the mechanochemical patterning theory. During embryogenesis, biological tissues gradually increase their complexity by self-organised creation of diverse chemical and mechanical patterns. Detailed mechanisms driving and controlling these patterns are not well understood. Previous theories mostly assume that these patterns are driven by chemical processes. Based on these theories, mechanical patterns are usually considered being mainly determined by chemical pre-patterns. However, experimental evidence for these theories is sparse, and several inconsistencies have been discovered. Furthermore, an increasing amount of data shows that tissue mechanics plays an important role in pattern formation. In this study, we present 3D computer simulations of evolving tissues to investigate the capacity of mechanochemical interactions for pattern formation. We show that even simple interactions between tissue mechanics and tissue chemistry spontaneously lead to robust chemical and mechanical pattern formation. We additionally demonstrate that main contradictions arising in the framework of purely chemical theories are naturally and automatically resolved using the mechanochemical patterning theory. The presented modelling approach can be used to combine simulations with recent experimental developments, to help unravel one of the big mysteries in biology: The mechanisms of self-organised pattern formation during embryogenesis.

Hydra ’s almost unlimited regenerative potential is based on Wnt signaling, but so far it is unknown how the injury stimulus is transmitted to discrete patterning fates in head and foot regenerates. We previously identified mitogen-activated protein kinases (MAPKs) among the earliest injury response molecules in Hydra head regeneration. Here, we show that three MAPKs—p38, c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases (ERKs)—are essential to initiate regeneration in Hydra, independent of the wound position. Their activation occurs in response to any injury and requires calcium and reactive oxygen species (ROS) signaling. Phosphorylated MAPKs hereby exhibit cross talk with mutual antagonism between the ERK pathway and stress-induced MAPKs, orchestrating a balance between cell survival and apoptosis. Importantly, Wnt3 and Wnt9/10c, which are induced by MAPK signaling, can partially rescue regeneration in tissues treated with MAPK inhibitors. Also, foot regenerates can be reverted to form head tissue by a pharmacological increase of β-catenin signaling or the application of recombinant Wnts. We propose a model in which a β-catenin-based stable gradient of head-forming capacity along the primary body axis, by differentially integrating an indiscriminate injury response, determines the fate of the regenerating tissue. Hereby, Wnt signaling acquires sustained activation in the head regenerate, while it is transient in the presumptive foot tissue. Given the high level of evolutionary conservation of MAPKs and Wnts, we assume that this mechanism is deeply embedded in our genome.

Motivated by recent experimental findings, we propose a novel mechanism of embryonic pattern formation based on coupling of tissue curvature with diffusive signaling by a chemical factor. We derive a new mathematical model using energy minimization approach and show that the model generates a variety of morphogen and curvature patterns agreeing with experimentally observed structures. The mechanism proposed transcends the classical Turing concept which requires interactions between two morphogens with a significantly different diffusivity. Our studies show how biomechanical forces may replace the elusive long-range inhibitor and lead to formation of stable spatially heterogeneous structures without existence of chemical prepatterns. We propose new experimental approaches to decisively test our central hypothesis that tissue curvature and morphogen expression are coupled in a positive feedback loop.

Seabirds have increasingly encountered offshore wind farms (OWFs) in European waters in the past 10 years, resulting in potential conflicts with offshore foraging areas. During the breeding season, seabirds are restricted in their choice of foraging habitat and are under increased pressure to find enough prey to raise their offspring. However, information on the individual reactions of seabirds towards OWFs during the breeding season is lacking. Three OWFs located 23–35 km north of the island of Helgoland have operated since October 2015. We studied their possible effects on locally breeding common guillemots (Uria aalge) using GPS tracking. GPS tags were deployed on 12 breeding guillemots from Helgoland for 8–26 days during 2016–2017. Most individuals avoided the OWFs, but one individual in each year briefly entered the OWFs on two or three occasions. Using a point process model, we revealed a 63% reduction in the resource selection of the OWF areas compared with the surroundings (lower confidence interval (CI) = 79% reduction, upper CI = 36% reduction). Furthermore, OWF avoidance was increased to 75% when the turbine blades were rotating (lower CI = 93% reduction, upper CI = 11% reduction). Guillemots mainly approached the OWFs from their eastern edge when resting or diving, and rarely approached the areas when commuting. These results provide a detailed description of guillemot reactions to OWFs during the breeding season, and the first comprehensive analysis of OWF effects on this species based on telemetry data. The strong avoidance effect for guillemots during the breeding season indicates the need to consider the presence of OWFs when interpreting future trends in the abundance and breeding success of this species.

Tissue morphogenesis comprises the self-organized creation of various patterns and shapes. Although detailed underlying mechanisms are still elusive in many cases, an increasing amount of experimental data suggests that chemical morphogen and mechanical processes are strongly coupled. Here, we develop and test a minimal model of the axis-defining step (i.e., symmetry breaking) in aggregates of the Hydra polyp. Based on previous findings, we combine osmotically driven shape oscillations with tissue mechanics and morphogen dynamics. We show that the model incorporating a simple feedback loop between morphogen patterning and tissue stretch reproduces a wide range of experimental data. Finally, we compare different hypothetical morphogen patterning mechanisms (Turing, tissue-curvature, and self-organized criticality). Our results suggest the experimental investigation of bigger (i.e., multiple head) aggregates as a key step for a deeper understanding of mechanochemical symmetry breaking in Hydra.

During embryogenesis, chemical (morphogen) and mechanical patterns develop within tissues in a self-organized way. More than 60 years ago, Turing proposed his famous reaction-diffusion model for such processes, assuming chemical interactions as the main driving force in tissue patterning. However, experimental identification of corresponding molecular candidates is still incomplete. Recent results suggest that beside morphogens, also tissue mechanics play a significant role in these patterning processes. Combining continuous finite strain with discrete cellular tissue models, we present and numerically investigate mechanochemical processes, in which morphogen dynamics and tissue mechanics are coupled by feedback loops. We consider three different mechanical cues involved in such feedbacks: strain, stress, and compression. Based on experimental results, for each case, we present a feedback loop spontaneously creating robust mechanochemical patterns. In contrast to Turing-type models, simple mechanochemical interaction terms are sufficient to create de novo patterns. Our results emphasize mechanochemical processes as possible candidates controlling different steps of embryogenesis. To motivate further experimental research discovering related mechanisms in living tissues, we also present predictive in silicio experiments. Reviewer 1 - Marek Kimmel; Reviewer 2 - Konstantin Doubrovinski (nominated by Ned Wingreen); Reviewer 3 - Jun Allard (nominated by William Hlavacek).