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Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned and initially identical (...) |
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It has been convincingly shown that peptides play important roles in the regulation and maintenance of a variety of tissues and organs in living animals. However, little is known concerning the potential role of peptides as signaling molecules in developmental processes. In Hydra, there is circumstantial evidence that small diffusible molecules act as morphogens in the regulation of patterning processes. In order to view the entire spectrum of peptide signaling molecules, we initiated a project aiming at the systematic identification of (...) |
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This essay provides an introduction to the terminology, concepts, methods, and challenges of image‐based modeling in biology. Image‐based modeling and simulation aims at using systematic, quantitative image data to build predictive models of biological systems that can be simulated with a computer. This allows one to disentangle molecular mechanisms from effects of shape and geometry. Questions like “what is the functional role of shape” or “how are biological shapes generated and regulated” can be addressed in the framework of image‐based systems (...) |
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In 1972, we proposed a theory of biological pattern formation in which concentration maxima of pattern forming substances are generated through local self- enhancement in conjunction with long range inhibition. Since then, much evidence in various developmental systems has confirmed the importance of autocatalytic feedback loops combined with inhibitory interaction. Examples are found in the formation of embryonal organizing regions, in segmentation, in the polarization of individual cells, and in gene activation. By computer simulations, we have shown that the theory (...) |
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In three recent articles it was shown that β‐catenin is crucial for the establishment and the maintenance of the overall polarity and especially for the character ‘posterior’ in planarians. If the transcription of the β‐catenin gene was silenced by RNA interference, the overall polarity is lost, and in regenerating fragments a posterior blastema displays anterior characters by forming eyes and anterior ganglia. An attempt is made to integrate these new data, well‐known older observations, and observations from other regenerating systems into (...) |
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Retinoids are low molecular weight, lipophilic derivatives of vitamin A which have a profound effect upon the development of a diverse array of animals. Here, I review these effects on Invertebrates: a colonial hydroid, a colonial ascidian, and Vertebrates: the regenerating amphibian limb, the developing chick limb bud, the regenerating amphibian tail, the anteroposterior axis of the early embryo, the developing chick embryo skin. There is a striking uniformity of effect of retinoids on pattern formation when applied to these diverse (...) |
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Proponents of mechanistic explanations have recently proclaimed that all explanations in the neurosciences appeal to mechanisms. The purpose of the paper is to critically assess this statement and to develop an integrative account that connects a large range of both mechanistic and dynamical explanations. I develop and defend four theses about the relationship between dynamical and mechanistic explanations: that dynamical explanations are structurally grounded, that they are multiply realizable, possess realizing mechanisms and provide a powerful top-down heuristic. Four examples shall (...) No categories |
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Proper wiring of the nervous system requires tight control of the number of nerve terminals that innervate a target tissue. Recent work by Deppmann et al.,1 now suggests that this is achieved by feedback‐mediated neuronal competition for target‐derived survival cues. The authors' model is inspired by the theory for pattern formation based on self‐activation and lateral inhibition, proposed by Meinhardt and Gierer more than 30 years ago.2 BioEssays 30:929–933, 2008. © 2008 Wiley Periodicals, Inc. |
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We propose a model mechanism for the initiation and spatial positioning of teeth primordia in the alligator, Alligator mississippiensis. Detailed embryological studies by Westergaard and Ferguson have shown that jaw growth plays a crucial role in the developmental patterning of the tooth initiation process. Based on biological data we develop a dynamic patterning mechanism, which crucially includes domain growth. The mechanism can reproduce the spatial pattern development of the first seven teeth primordia in each half jaw of A. mississippiensis. The (...) |
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Embryonic development and adult tissue homeostasis are controlled through activation of intracellular signal transduction pathways by extracellular growth factors. In the past, signal transduction has largely been regarded as a linear process. However, more recent data from large‐scale and high‐throughput experiments indicate that there is extensive cross‐talk between individual signaling cascades leading to the notion of a signaling network. The behavior of such complex networks cannot be predicted by simple intuitive approaches but requires sophisticated models and computational simulations. The purpose (...) |
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Network motifs are small patterns of connections, found over‐represented in gene regulatory networks. An example is the negative feedback loop (e.g. factor A represses itself). This opposes its own state so that when ‘on’ it tends towards ‘off’ – and vice versa. Here, we argue that such self‐opposition, if considered dimensionlessly, is analogous to the liar paradox: ‘This statement is false’. When ‘true’ it implies ‘false’ – and vice versa. Such logical constructs have provided philosophical consternation for over 2000 years. (...) |
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Since Darwin's theory of evolution by natural selection, the idea of descent with modification came to dominate systematics, and so the study of morphology became subgugated to the reconstruction of phylogenies. Reinstating the organism in the theory of evolution (Ho & Saunders, 1979; Webster & Goodwin, 1982) leads to a project inrational taxonomy (Ho, 1986, 1988a), which attempts to classify biological forms on the basis of transformations on a given dynamical structure.Does rational taxonomy correspond to thenatural system that Linnaeus and (...) |
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Morphogenesis is a key process in developmental biology. An important issue is the understanding of the generation of shape and cellular organisation in tissues. Despite of their great diversity, morphogenetic processes share common features. This work is an attempt to describe this diversity using the same formalism based on a cellular description. Tissue is seen as a multi-cellular system whose behaviour is the result of all constitutive cells dynamics. Morphogenesis is then considered as a spatiotemporal organization of cells activities. We (...) |
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The control of pattern formation and the significance of gradients is reconsidered on the basis of the concept of cell sociology (which takes into account continuous exchange of information between cells and the possibility of autonomous progression in differentiation). Not all traits of a pattern are imposed by a single prepattern, which would be an organized molecular framework or a gradient. Patterns are unfolded in steps; these are readjustments of a cell population to intrinsic and extrinsic changes in cell activities. (...) |
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Scaling of pattern with size has been described and studied for over a century, yet its molecular basis is understood in only a few cases. In a recent, elegant study, Inomata and colleagues proposed a new model explaining how bone morphogenic protein (BMP) activity gradient scales with embryo size in the early Xenopus laevis embryo. We discuss their results in conjunction with an alternative model we proposed previously. The expansion‐repression mechanism (ExR) provides a conceptual framework unifying both mechanisms. Results of (...) |
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Possible effects of interaction (cross-talk) between signaling pathways is studied in a system of Reaction–Diffusion (RD) equations. Furthermore, the relevance of spontaneous neurite symmetry breaking and Turing instability has been examined through numerical simulations. The interaction between Retinoic Acid (RA) and Notch signaling pathways is considered as a perturbation to RD system of axon-forming potential for N2a neuroblastoma cells. The present work suggests that large increases to the level of RA–Notch interaction can possibly have substantial impacts on neurite outgrowth and (...) |
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The introductory personal remarks refer to my motivations for choosing research projects, and for moving from physics to molecular biology and then to development, with Hydra as a model system. Historically, Trembley’s discovery of Hydra regeneration in 1744 was the begin¬ning of developmental biology as we understand it, with passionate debates about preformation versus de novo generation, mechanisms versus organisms. In fact, seemingly conflicting bottom-up and top-down concepts are both required in combination to understand development. In modern terms, this means (...) |
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In the last decade, Systems Biology has emerged as a conceptual and explanatory alternative to reductionist-based approaches in molecular biology. However, the foundations of this new discipline need to be fleshed out more carefully. In this paper, we claim that a relational ontology is a necessary tool to ground both the conceptual and explanatory aspects of Systems Biology. A relational ontology holds that relations are prior—both conceptually and explanatory—to entities, and that in the biological realm entities are defined primarily by (...) |
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Evo-Devo exhibits a plurality of scientific “cultures” of practice and theory. When are the cultures acting—individually or collectively—in ways that actually move research forward, empirically, theoretically, and ethically? When do they become imperialistic, in the sense of excluding and subordinating other cultures? This chapter identifies six cultures – three /styles/ (mathematical modeling, mechanism, and history) and three /paradigms/ (adaptationism, structuralism, and cladism). The key assumptions standing behind, under, or within each of these cultures are explored. Characterizing the internal structure of (...) |
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A strong motivation for the human genome project was to relate biological features to the structure and function of small sets of genes, and ideally to individual genes. However, it is now increasingly realized that many problems require a "systems" approach emphasizing the interplay of large numbers of genes, and the involvement of complex networks of gene regulation. This implies a new emphasis on integrative, systems theoretical approaches. It may be called 'holistic' if the term is used without irrational overtones, (...) |
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Socioeconomic inequalities are functions not only of intrinsic differences between persons or groups, but also of the dynamics of their interactions. Inequalities can arise and become stabilized if there are advantages (such as generalized wealth including “human capital”) which are self-enhancing, whereas depletion of limiting resources is widely distributed. A recent theory of biological pattern formation has been generalized, adapted and applied to deal with this process. Applications include models for the non-Gaussian distribution of personal income and wealth, for overall (...) |
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