Fig 10 - uploaded by Lev Beloussov
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A scenario of the active increase of an imposed curvature. A) Passive convex side stretching and concave side compression caused by an external force. B) Active extension of a convex surface and contraction of a concave one directed towards hyper-restoration of perturbed stresses and accompanied by a flow of cell material towards a convex side (black arrows). Dashed contours depict the inversely oriented curvatures expected to be formed on the flanks of the central one (see text). C) Same mechanisms when attributed to a curved lip will promote the involution of cells from the convex to the concave side.
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A fundamental problem of morphogenesis is whether it presents itself as a succession of links that are each driven by its own specific cause-effect relationship, or whether all of the links can be embraced by a common law that is possible to formulate in physical terms. We suggest that a common biophysical background for most, if not all, morphogen...
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... is of primary importance for epithelial buckling and can be termed the curvature increase (CI) feedback. This feedback is triggered by the slight bending (that is, increase in the local curvature) of an elastic cell layer by any external force (usually a lat- eral pressure). Such a bending will stretch the convex and shrink the concave surface ( fig. 10A). The presence of the corresponding stresses can be confirmed by the conver- sion of a layer back to its initial shape if it were released no later than a few minutes after being artificially bent. However, if maintaining a sample of embryonic tissue in a deformed state for several dozens of minutes, the oppo- site reaction will occur, ...
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... of the HR model, which predicts that a convex surface of a sample will (hyper)release its stretching by inserting new material, whereas a concave surface tends to engulf an excessive amount of its shrunken surface to (hyper)restore its initial, tensed state. Both processes may be accompanied by a flow of material from the concave to convex side ( fig. 10B, arrows) and are directed towards the increase in curvature. In addition, the active bending will initiate the oppositely directed bucklings onto its flanks ( fig. 10B, dashed contours), and the entire series of folds can commonly be formed. Lastly, if a curved part of the epithelia presents a fold (or a "lip" by ubiquitous termi- ...
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... an excessive amount of its shrunken surface to (hyper)restore its initial, tensed state. Both processes may be accompanied by a flow of material from the concave to convex side ( fig. 10B, arrows) and are directed towards the increase in curvature. In addition, the active bending will initiate the oppositely directed bucklings onto its flanks ( fig. 10B, dashed contours), and the entire series of folds can commonly be formed. Lastly, if a curved part of the epithelia presents a fold (or a "lip" by ubiquitous termi- nology) by itself, the same tendencies will initiate a flow of cells from the convex to the concave surface, which is termed an "involution" (fig. 10C). Another important HR model-based ...
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... bucklings onto its flanks ( fig. 10B, dashed contours), and the entire series of folds can commonly be formed. Lastly, if a curved part of the epithelia presents a fold (or a "lip" by ubiquitous termi- nology) by itself, the same tendencies will initiate a flow of cells from the convex to the concave surface, which is termed an "involution" (fig. 10C). Another important HR model-based feedback is un- folded in 3D space. This type of feedback deals with toroidal bodies to which a number of embryonic struc- tures and, first of all, the circular blastoporal lips, are similar. As shown by incision experiments [16], the surface of the lips is under tension. However, it is known from me- ...
Citations
... In particular, these studies provide the basis for the organism-centered theory, such as Extended Evolutionary synthesis (EES) (see Laland et al., 2014). The postulates of the unified theory of embryonic development, which shows that the morphogenesis is a multi-level process including selforganizing steps and obeying general patterns of nature in mechanisms and mechanical forces become more precise and profound (Beloussov, 2012a(Beloussov, , 2012b(Beloussov, , 2013(Beloussov, , 2015. More and more data display that the morphogenesis is in all cases implemented by similar "molecular machine" and evolutionary distinctions are caused by the shifts (in time and space) of the sequences of molecular processes (see Korochkin, 2002aKorochkin, , 2002b. ...
Macroevolution, or evolution of superspecies taxa is the process of transformation of “organismal” life flows on the Earth during its geological history. In the present study, this process is analyzed with using the system and evolutionarily‒ecological approaches. Based on modern paleontological, evolutionary biological, molecular, and genetic data, mostly on vertebrates and hominins, the major factors and patterns of macroevolution and also the role of macroevolution in the biosphere evolution are discussed. The fundamental bases of the concept of macroevolution, the problems of methodology and methods of the study of organismal evolution are considered. It is shown that the processes at the macroevolutionary level agree with the epigenetic theory of evolution.
... Our ultimate goal, however, is the programming of shape by specifying organs and their topological relationships, instead of attempting to micromanage the construction at the 'machine language' level [129,130]. Here, we have discussed a complementary, top-down approach, which can encompass the known molecular elements that implement pattern formation: chemical gradients [131][132][133][134], physical forces [135][136][137] and bioelectrical signalling [108,115,[138][139][140]. Numerous examples of pattern formation exist [141], in which spatial order is generated by emergence from collective low-level dynamics. ...
It is widely assumed in developmental biology and bioengineering that optimal understanding and control of complex living systems follows from models of molecular events. The success of reductionism has overshadowed attempts at top-down models and control policies in biological systems. However, other fields, including physics, engineering and neuroscience, have successfully used the explanations and models at higher levels of organization, including least-action principles in physics and controltheoretic models in computational neuroscience. Exploiting the dynamic regulation of pattern formation in embryogenesis and regeneration requires new approaches to understand how cells cooperate towards large-scale anatomical goal states. Here, we argue that top-down models of pattern homeostasis serve as proof of principle for extending the current paradigm beyond emergence and molecule-level rules. We define top-down control in a biological context, discuss the examples of how cognitive neuroscience and physics exploit these strategies, and illustrate areas in which they may offer significant advantages as complements to the mainstream paradigm. By targeting system controls at multiple levels of organization and demystifying goal-directed (cybernetic) processes, top-down strategies represent a roadmap for using the deep insights of other fields for transformative advances in regenerative medicine and systems bioengineering. © 2016 The Author(s) Published by the Royal Society. All rights reserved.
... To begin to mechanistically link individual cell behaviors (such as those regulated by GJ-mediated signals) to large-scale anatomical outcomes, we next constructed an agent-based model of cell signaling and morphogenesis. Our model focused on cell migration and cell-cell signaling, as these are clearly important for implementing different morphogenetic outcomes [95][96][97], and also known to be regulated by GJ connectivity [98] and bioelectric properties of neighboring cells [99]. ...
The shape of an animal body plan is constructed from protein components encoded by the genome. However, bioelectric networks composed of many cell types have their own intrinsic dynamics, and can drive distinct morphological outcomes during embryogenesis and regeneration. Planarian flatworms are a popular system for exploring body plan patterning due to their regenerative capacity, but despite considerable molecular information regarding stem cell differentiation and basic axial patterning, very little is known about how distinct head shapes are produced. Here, we show that after decapitation in G. dorotocephala, a transient perturbation of physiological connectivity among cells (using the gap junction blocker octanol) can result in regenerated heads with quite different shapes, stochastically matching other known species of planaria (S. mediterranea, D. japonica, and P. felina). We use morphometric analysis to quantify the ability of physiological network perturbations to induce different species-specific head shapes from the same genome. Moreover, we present a computational agent-based model of cell and physical dynamics during regeneration that quantitatively reproduces the observed shape changes. Morphological alterations induced in a genomically wild-type G. dorotocephala during regeneration include not only the shape of the head but also the morphology of the brain, the characteristic distribution of adult stem cells (neoblasts), and the bioelectric gradients of resting potential within the anterior tissues. Interestingly, the shape change is not permanent; after regeneration is complete, intact animals remodel back to G. dorotocephala-appropriate head shape within several weeks in a secondary phase of remodeling following initial complete regeneration. We present a conceptual model to guide future work to delineate the molecular mechanisms by which bioelectric networks stochastically select among a small set of discrete head morphologies. Taken together, these data and analyses shed light on important physiological modifiers of morphological information in dictating species-specific shape, and reveal them to be a novel instructive input into head patterning in regenerating planaria.
... As we have already mentioned, forces can be also generated by contracting cells (Harris et al., 1981) and can appear as a result of osmosis (Beloussov, 2008). Since the ensuing mechanical interactions produce a feedback on cell behavior (Beloussov, 2013) they may also affect the tasks conventionally attributed to bio-chemical morphogenes (Nelson et al., 2005;Pourquié, 2011). ...
... The formation of mesodermal somites was also linked with (columnar) polarization of cells in the axial mesoderm (Belintsev, Beloussov, & Zaraisky, 1987) and in the proposed reaction-diffusion type model long-range mechanical interactions were modelled as an influence of the 'whole' upon the state of an individual cell. A related model of the mechanical feedback based on the 'hyper-restoration' hypothesis (Beloussov, 2013) was proposed in Taber (2009). ...
Segmentation is a characteristic feature of the vertebrate body plan. The prevailing paradigm explaining its origin is the ‘clock and wave-front’ model, which assumes that the interaction of a molecular oscillator (clock) with a traveling gradient of morphogens (wave) pre-defines spatial periodicity. While many genes potentially responsible for these processes have been identified, the precise role of molecular oscillations and the mechanism leading to physical separation of the somites remain elusive. In this paper we argue that the periodicity along the embryonic body axis anticipating somitogenesis is controlled by mechanical rather than bio-chemical signaling. Using a prototypical model we show that regular patterning can result from a mechanical instability induced by differential strains developing between the segmenting mesoderm and the surrounding tissues. The main ingredients of the model are the assumptions that cell–cell adhesions soften when overstretched, and that there is an internal length scale defining the cohesive properties of the mesoderm. The proposed mechanism generates a robust number of segments without dependence on genetic oscillations.
The laboratory is engaged in morphomechanics—the study of self-organization of mechanical
forces that create the shape and structure of the embryonic primordia. As part of its work, the laboratory
described pulsating modes of mechanical stresses in hydroids, identified and mapped mechanical stresses in
the tissues of amphibian embryos, and studied morphogenetic reorganization caused by the relaxation and
reorientation of tensions. The role of mechanical stresses in maintaining the orderly architectonics of the
embryo is shown. Mechano-dependent genes are detected. Microstrains of embryonic tissues and stress gradients
associated with them are described. A model of hyper-recovery of mechanical stresses as a possible
driving force of morphogenesis is proposed.
We start from reviewing several ubiquitous approaches to morphogenesis and argue that for a more adequate presentation of morphogenesis, they should be replaced by explanatory constructions based upon the self-organization theory (SOT). The first step on this way will be in describing morphogenetic events in terms of the symmetry theory, to distinguish the processes driven either toward increase or toward decrease of the symmetry order and to use Curie principle as a clue. We will show that the only way to combine this principle with experimental data is to conclude that morphogenesis passes via a number of instabilities. The latter, in their turn, point to the domination of nonlinear regimes. Accordingly, we come to the realm of SOT and give a survey of the dynamic modes which it provides. By discussing the physical basis of embryonic self-organization, we focus ourselves on the role of mechanical stresses. We suggest that many (although no all) morphogenetic events can be regarded as retarded relaxations of previously accumulated elastic stresses toward a restricted number of metastable energy wells.
An attempt is made to reconstruct the natural successions of the developmental events on the basis of a common mechanically based trend. It is formulated in terms of a hyper-restoration (HR) hypothesis claiming that embryonic tissue responds to any external deforming force by generating its own one, directed toward the restoration of the initial stress value, but as a rule overshooting it in the opposite side. We give a mathematical formulation of this model, present a number of supporting evidences, and describe several HR-driven feedbacks which may drive forth morphogenesis. We use this approach for reconstructing in greater detail the gastrulation of the embryos from different taxonomic groups. Also, we discuss the application of this model to cytotomy, ooplasmic segregation, and shape complication of tubular rudiments (taking hydroid polyps as examples). In addition, we review the perspectives for applying morphomechanical approach to the problem of cell differentiation.
A major goal of regenerative medicine and bioengineering is the regeneration of complex organs, such as limbs, and the capability to create artificial constructs (so-called biobots) with defined morphologies and robust self-repair capabilities. Developmental biology presents remarkable examples of systems that self-assemble and regenerate complex structures toward their correct shape despite significant perturbations. A fundamental challenge is to translate progress in molecular genetics into control of large-scale organismal anatomy, and the field is still searching for an appropriate theoretical paradigm for facilitating control of pattern homeostasis. However, computational neuroscience provides many examples in which cell networks - brains - store memories (e.g., of geometric configurations, rules, and patterns) and coordinate their activity towards proximal and distant goals. In this Perspective, we propose that programming large-scale morphogenesis requires exploiting the information processing by which cellular structures work toward specific shapes. In non-neural cells, as in the brain, bioelectric signaling implements information processing, decision-making, and memory in regulating pattern and its remodeling. Thus, approaches used in computational neuroscience to understand goal-seeking neural systems offer a toolbox of techniques to model and control regenerative pattern formation. Here, we review recent data on developmental bioelectricity as a regulator of patterning, and propose that target morphology could be encoded within tissues as a kind of memory, using the same molecular mechanisms and algorithms so successfully exploited by the brain. We highlight the next steps of an unconventional research program, which may allow top-down control of growth and form for numerous applications in regenerative medicine and synthetic bioengineering.
This book outlines a unified theory of embryonic development, assuming morphogenesis to be a multi-level process including self-organizing steps while also obeying general laws. It is shown how molecular mechanisms generate mechanical forces, which in the long run lead to morphological changes. Questions such as how stress-mediated feedback acts at the cellular and supra-cellular levels and how executive and regulatory mechanisms are mutually dependent are addressed, while aspects of collective cell behavior and the morphogenesis of plants are also discussed. The morphomechanical approach employed in the book is based on the general principles of self-organization theory.
Regular patterns of mechanical stresses are perfectly expressed on the macromorphological level in the embryos of all taxonomic groups studied in this respect. Stress patterns are characterized by the topological invariability retained during prolonged time periods and drastically changing in between. After explanting small pieces of embryonic tissues, they are restored within several dozens minutes. Disturbance of stress patterns in developing embryos irreversibly breaks the long-range order of subsequent development. Morphogenetically important stress patterns are established by three geometrically different modes of cell alignment: parallel, perpendicular, and oblique. The first of them creates prolonged files of actively elongated cells. The second is responsible for segregation of an epithelial layer to the domains of columnar and flattened cells. The model of this process, demonstrating its scaling capacities, is described. The third mode which follows the previous one is responsible for making the curvatures. It is associated with formation of “cell fans,” the universal devices for shapes formation due to slow relaxation of the stored elastic energy.
