Development is a process whereby a relatively unspecified system comprised of loosely connected lower level parts becomes organized into a coherent, higher-level agency. Its temporal corollaries are growth, increasingly deterministic behavior, and a progressive reduction of developmental potential. During immature stages with relatively low specification and high potential, development is largely controlled by local interactions from the “bottom-up,” whereas during more highly specified stages with reduced potential, emergent autocatalytic processes exert “top-down” control. Robert Ulanowicz has shown that this phenomenology of (...) ascendency follows thermodynamic principles and can be described quantitatively using information theory, providing a general theory of development. However, the theory has not found a wide audience among developmental biologists, as genetic determinism encourages the popular reductionistic perception that ontogeny is controlled entirely by molecular mechanisms that exert efficient causality from the bottom-up. Nonetheless, measurements of metabolic rates and mRNA complexity in developing embryos, as well as functional analyses of gene regulatory systems, indicate that ontogeny fits the paradigm of developmental ascendency. Beyond informing biomedical research and the interpretation of large datasets obtained by systems-biological approaches, developmental ascendency helps explain the origin of life, and, being independent of scale, provides an overarching explanation for phylogenetic change that contextualizes Darwinian evolution. (shrink)

The “DNA is a program” metaphor is still widely used in Molecular Biology and its popularization. There are good historical reasons for the use of such a metaphor or theoretical model. Yet we argue that both the metaphor and the model are essentially inadequate also from the point of view of Physics and Computer Science. Relevant work has already been done, in Biology, criticizing the programming paradigm. We will refer to empirical evidence and theoretical writings in Biology, although our arguments (...) will be mostly based on a comparison with the use of differential methods (in Molecular Biology: a mutation or alike is observed or induced and its phenotypic consequences are observed) as applied in Computer Science and in Physics, where this fundamental tool for empirical investigation originated and acquired a well-justified status. In particular, as we will argue, the programming paradigm is not theoretically sound as a causal(as in Physics) or deductive(as in Programming) framework for relating the genome to the phenotype, in contrast to the physicalist and computational grounds that this paradigm claims to propose. (shrink)

Studies of chimeras and in vivo development demonstrate that cell lineages are often quite variable, apparently in response to chance perturbations. This points to an apparent contradiction: although individual cells are the units of genetic information and differentiation, not all cellular events need be precise for the development of functional organisms. The social organization of ants can serve as a metaphor that helps understand the mechanisms that underlie such development. Ants suggest that continued cellular interactions and environmental conditions could specify (...) the proportion and general location of specialized units. Leaf venation is used as a concrete example of this general principle. A signal produced continuously by all cells specifies a requirement for vein differentiation. The cells that respond by differentiation then transport the signal away from the leaf; this removal acting as a feedback indicating that the requirement is being met. Because transport increases during vein differentiation, early initiation occurs in excess and vein ‘competition’ for the signal assures an acceptable outcome. Such specification would be robust since it does not depend on events in any single cell, and chance events, rather than being corrected or reversed, may be built upon in reaching an expected, collective phenotype. The absence of detailed information preceding development distinguishes this hypothesis from the common alternatives of a program or blueprint. Collective specification would have important implications for developmental plasticity and evolution. BioEssays 25:897–903, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The majority of G protein-coupled receptors (GPCRs) self-assemble in the form dimeric/oligomeric complexes along the plasma membrane. Due to the molecular interactions they participate, GPCRs can potentially provide the framework for discriminating a wide variety of intercellular signals, as based on some kind of combinatorial receptor codes. GPCRs can in fact transduce signals from the external milieu by modifying the activity of such intracellular proteins as adenylyl cyclases, phospholipases and ion channels via interactions with specific G-proteins. However, in spite of (...) the number of cell functions they can actually control, both GPCRs and their associated signal transduction pathways are extremely well conserved, for only a few alleles with null or minor functional alterations have so far been found. This would seem to suggest that, beside a mechanism for DNA repairing, there must be another level of quality control that may help maintaining GPCRs rather stable throughout evolution. We propose here receptor oligomerization to be a basic molecular mechanism controlling GPCRs redundancy in many different cell types, and the plasma membrane as the first hierarchical cell structure at which selective categorical sensing may occur. Categorical sensing can be seen as the cellular capacity for identifying and ordering complex patterns of mixed signals out of a contextual matrix, i.e., the recognition of meaningful patterns out of ubiquitous signals. In this context, redundancy and degeneracy may appear as the required feature to integrate the cell system into functional units of progressively higher hierarchical levels. (shrink)

Waddington’s experiments on genetic assimilation showed that selection on environmentally induced phenotypic variants can cause inherited evolutionary changes in the phenotype. We have recently extended this work by demonstrating that it is possible to select for a polyphenism in a monophenic species . We found that a mutation in the juvenile hormone regulatory pathway in Manduca sexta enabled heat stress to reveal a hidden reaction norm of larval coloration. Artificial selection for increased color change in response to heat-shock resulted in (...) the genetic accommodation of a black/green larval color polyphenism, caused by an environment-sensitive threshold switch mediated by the endocrine system. (shrink)

The robustness of biological processes to perturbations has so far been mainly explored in unicellular organisms; multicellular organisms have been studied for developmental processes or in the special case of redundancy between gene duplicates. Here we explore the robustness of cell biological mechanisms of multicellular organisms in an evolutionary context. We propose that the reuse of similar cell biological mechanisms in different cell types of the same organism has evolutionary implications: (1) the maintenance of apparently redundant mechanisms over evolutionary time (...) may in part be explained by their differential requirement in various cell types; (2) the relative requirement for two alternative mechanisms may evolve among homologous cells in different organisms. We present examples of cell biological processes, such as centrosome separation in prophase, spindle formation or cleavage furrow positioning, that support the first proposition. We propose experimental tests of these hypotheses. (shrink)