Mechanically based generative laws of morphogenesis

A deep (although at the first glance na?ve) question which may be addressed to embryonic development is why during this process quite definite and accurately reproduced successions of precise and complicated shapes are taking place, or why, in several cases, the result of development is highly precise in spite of an extensive variability of intermediate stages. This problem can be attacked in two different ways. One of them, up to now just slightly employed, is to formulate robust macroscopic generative laws from which the observed successions of shapes could be derived. Another one, which dominates in modern embryology, regards the development as a succession of highly precise 'micropatterns', each of them arising due to the action of specific factors, having, as a rule, nothing in common with each other. We argue that the latter view contradicts a great bulk of firmly established data and gives no satisfactory answers to the main problems of development. Therefore we intend to follow the first way. By doing this, we regard developing embryos as self-organized systems transpierced by feedbacks among which we pay special attention to those linked with mechanical stresses (MS). We formulate a hypothesis of so-called MS hyper-restoration as a common basis for the developmentally important feedback loops. We present a number of examples confirming this hypothesis and use it for reconstructing prolonged chains of developmental events. Finally, we discuss the application of the same set of assumptions to the first steps of egg development and to the internal differentiation of embryonic cells.     

Generative rules for the morphogenesis of epithelial tubes.

A finite elements model imitating the morphogenesis of smoothly curved tubular epithelial rudiments is suggested. It is based upon the experimentally proved assumption of the lateral (tangential) pressure between adjacent epithelial cells. The main idea of the model is that under a non-zero local curvature the lateral cell-cell pressure acquires the radial components which are absent under zero curvature. In the framework of the model we investigate the roles of initial geometry, the different coefficients relating the local curvatures and radial cell shifts, and of visco-elastical cell-cell linkages in the shaping process. We also employ the different temporal regimes (both periodical and constant) of the lateral pressure exerted and the different overall durations of the modelling. As a result, we get a set of biologically realistical shapes, almost all of them belonging to the same basical "trefoiled" archetype. Among the variables explored, shaping was most affected by the changes in visco-elastical coefficients, in the temporal regimes and in the overall duration of the modelling. The model shows that rather complicated and realistical shapes of epithelial rudiments can be obtained without assuming any initial regional differences inside cell layers. The model may be useful for understanding the principles underlying both genetical and epigenetical regulation of the morphogenesis.     

Abnormal development of floral meristem triggers defective morphogenesis of generative system in transgenic tomatoes

Parthenocarpy and fruit malformations are common among independent transgenic tomato lines, expressing genes encoding different pathogenesis-related (PR) protein and antimicrobal peptides. Abnormal phenotype developed independently of the expression and type of target genes, but distinctive features during flower and fruit development were detected in each transgenic line. We analyzed the morphology, anatomy, and cytoembryology of abnormal flowers and fruits from these transgenic tomato lines and compared them with flowers and fruits of wild tomatoes, line YaLF used for transformation, and transgenic plants with normal phenotype. We confirmed that the main cause of abnormal flower and fruit development was the alterations of determinate growth of generative meristem. These alterations triggered different types of anomalous growth, affecting the number of growing ectopic shoots and formation of new flowers. Investigation of the ovule ontogenesis did not show anomalies in embryo sac development, but fertilization did not occur and embryo sac degenerated. Nevertheless, the ovule continued to differentiate due to proliferation of endothelium cells. The latter substituted embryo sac and formed pseudoembryonic tissue. This process imitated embryogenesis and stimulated ovary growth, leading to the development of parthenocarpic fruit. We demonstrated that failed fertilization occurred due to defective male gametophyte formation, which was manifested in blocked division of the nucleus in the microspore and arrest of vegetative and generative cell formation. Maturing pollen grains were overgrown microspores, not competent for fertilization but capable to induce proliferation of endothelium and development of parthenocarpic ovary. Thus, our study provided new data on the structural transformations of reproductive organs during development of parthenocarpic fruits in transgenic tomato.     

General generative principles

In search of general generative principles I start from the postulate of a reality which comprises both materialistic and psychic aspects. This overall reality, described by others as the world of archetypes, is not directly accessible to sensory perception. Yet, by studying archetypical manifestations, it is possible to distinguish different structures or generative principles in it. Comparison of three models, which depict developmental processes in different disciplines, shows that they have the same basic structure. The effects of the archetypes involved can be described as four general generative principles: 1st the principle of wholeness (connection and integration of conflicting opposites), 2nd the principle of complementation and compensation (periodic change of opposite influences); 3rd the enstructuring principle (relative stability or spatial aspect of a manifest structure), and 4th the principle of gesture (change or temporal aspect of that structure).     

On some generative orders of behaviour

The sociobiological fashion has for a long time discouraged the development of theories of the immediate causation of behaviour. It is only recently that new approaches are being developed to improve on the classical ethological theory originated by Lorenz and Tinbergen. One new departure is behavioural field theory (BFT) which brings back the concept of energy in behaviour, without being susceptible to the drawbacks of the energy or fuel concept of classical theory. In this paper the new theory is explained in some detail and it is shown to be illuminating, predictive and testable in examples of play-like and territorial behaviour.     

Learning generative models of molecular dynamics

We introduce three algorithms for learning generative models of molecular structures from molecular dynamics simulations. The first algorithm learns a Bayesian-optimal undirected probabilistic model over user-specified covariates (e.g., fluctuations, distances, angles, etc). L1 regularization is used to ensure sparse models and thus reduce the risk of over-fitting the data. The topology of the resulting model reveals important couplings between different parts of the protein, thus aiding in the analysis of molecular motions. The generative nature of the model makes it well-suited to making predictions about the global effects of local structural changes (e.g., the binding of an allosteric regulator). Additionally, the model can be used to sample new conformations. The second algorithm learns a time-varying graphical model where the topology and parameters change smoothly along the trajectory, revealing the conformational sub-states. The last algorithm learns a Markov Chain over undirected graphical models which can be used to study and simulate kinetics. We demonstrate our algorithms on multiple molecular dynamics trajectories.     

Information,complexity and generative replication

The established definition of replication in terms of the conditions of causality, similarity and information transfer is very broad. We draw inspiration from the literature on self-reproducing automata to strengthen the notion of information transfer in replication processes. To the triple conditions of causality, similarity and information transfer, we add a fourth condition that defines a “generative replicator” as a conditional generative mechanism, which can turn input signals from an environment into developmental instructions. Generative replication must have the potential to enhance complexity, which in turn requires that developmental instructions are part of the information that is transmitted in replication. Demonstrating the usefulness of the generative replicator concept in the social domain, we identify social generative replicators that satisfy all of the four proposed conditions.

Unifying generative and discriminative learning principles

Background  

The recognition of functional binding sites in genomic DNA remains one of the fundamental challenges of genome research. During the last decades, a plethora of different and well-adapted models has been developed, but only little attention has been payed to the development of different and similarly well-adapted learning principles. Only recently it was noticed that discriminative learning principles can be superior over generative ones in diverse bioinformatics applications, too.     

Palate morphogenesis

Summary Mesenchymal cells from the palate of mouse embryos at day 14.5 of gestation produce a minor population of stellate cells in culture. These cells are often bipolar and spindle-shaped with long cytoplasmic processes similar to neural-crest cells. Culturing of expiants of palatal mesenchyme enriched for this type of cell. Stellate cells were the first to migrate from the expiants, followed by fibroblast-like cells and then by squamous cells. The majority of the cells in the expiant were fibroblast-like. Squamous cells were present mostly in the anterior and mid-palate and least frequently in those from the posterior palate. They may represent tooth-germ epithelium. When pieces of palate were dissected out and cultured for enrichment of non-muscle contractile systems, most of the migrating cells were stellate. These may represent the highly migratory cells that are, in part, responsible for elevation of the palate shelf. Serotonin was measured in cultured mesenchymal cells from the palate. Its occurrence is consistent with regulation of movement of palate cells.     

Signaling in morphogenesis: transport cues in morphogenesis

Extracellular transport processes play critical roles in morphogenesis. While diffusive transport effects on morphogenesis are well illustrated in examples like blood capillary architecture and in cell morphogenetic responses to the local extracellular protein environment, the effects of fluid convection, although important in many developing and regenerating tissues, are not well understood. Convective forces are present whenever a hydrated tissue undergoes dynamic mechanical strain, and so convection could not only dominate the transport of large molecules like proteins, but might also serve as a mechanism for mechanosensing. The complex interdependence of mechanical forces, protein transport and extracellular morphogen gradients needs to be elucidated in a comprehensive way in order for the importance of transport on morphogenesis to be fully appreciated.     

Dendritic morphogenesis

Neurons are polarized cells with an axon and a dendritic arbor extending from the soma. Although the molecular mechanisms underlying axon guidance are rapidly being elucidated, those that regulate the orientation, morphology, and elaboration of dendritic processes are largely unknown. Several recent papers address these issues, and propose a set of molecular strategies that control dendrite development. This review discusses these papers and what they reveal to us about how cell signaling orchestrates neuronal form and connectivity during development.     

Cranial morphogenesis

The morphogenesis of the skull in the chick embryo is characterized by different steps, involving neural crest cell migration and appearance of chondroid tissue occupying the middle part of most of the ossification centres. This tissue represents the initial modality of the skeletogenic differentiation within the cephalic mesenchyme.