The genetic control paradigm in biology: What we say, and what we are entitled to mean.

We comment on the article by Keith Baverstock (2021) and provide critiques of the concepts of genetic control, genetic blueprint and genetic program.

The development of shape. Modular control of growth in the lepidopteran forewing.

The mechanisms by which tissues and organs achieve their final size and shape during development are largely unknown. Although we have learned much about the mechanisms that control growth, little is known about how those play out to achieve a structure's specific final size and shape. The wings of insects are attractive systems for the study of the control of morphogenesis, because they are perfectly flat and two-dimensional, composed of two closely appressed cellular monolayers in which morphogenetic processes can be easily visualized. The wings of Lepidoptera arise from imaginal disks whose structure is always perfectly congruent with that of the adult wing, so that it is possible to fate-map corresponding positions on the larval disk to those of the adult wing. Here we show that the forewing imaginal disks of Junonia coenia are subdivided into four domains, with characteristic patterns of expression of known patterning genes Spalt (Sal), Engrailed (En), and Cubitus interruptus (Ci). We show that DNA and protein synthesis, as well as mitoses, are spatially patterned in a domain-specific way. Knockdown of Sal and En using produced domain-specific reductions in the shape of the forewing. Knockdown of signaling pathways involved in the regulation of growth likewise altered the shape of the forewing in a domain-specific way. Our results reveal a multi-level regulation of forewing shape involving hormones and growth-regulating genes.

A developmental perspective of homology and evolutionary novelty.

The development and evolution of multicellular body plans is complex. Many distinct organs and body parts must be reproduced at each generation, and those that are traceable over long time scales are considered homologous. Among the most pressing and least understood phenomena in evolutionary biology is the mode by which new homologs, or "novelties" are introduced to the body plan and whether the developmental changes associated with such evolution deserve special treatment. In this chapter, we address the concepts of homology and evolutionary novelty through the lens of development. We present a series of case studies, within insects and vertebrates, from which we propose a developmental model of multicellular organ identity. With this model in hand, we make predictions regarding the developmental evolution of body plans and highlight the need for more integrative analysis of developing systems.

Competitive and Coordinative Interactions between Body Parts Produce Adaptive Developmental Outcomes.

Large-scale patterns of correlated growth in development are partially driven by competition for metabolic and informational resources. It is argued that competition between organs for limited resources is an important mesoscale morphogenetic mechanism that produces fitness-enhancing correlated growth. At the genetic level, the growth of individual characters appears independent, or "modular," because patterns of expression and transcription are often highly localized, mutations have trait-specific effects, and gene complexes can be co-opted as a unit to produce novel traits. However, body parts are known to interact over the course of ontogeny, and these reciprocal exchanges can be an important determinant of developmental outcomes. Genetic mechanisms underlie cell and tissue behaviors that allow organs to communicate with one another, but they also create evolutionarily adaptive competitive dynamics that are driven by physiological and biophysical processes. Advances in the understanding of competitive and closely related coordinative interactions across scales will complement existing research programs that emphasize the role of cellular mechanisms in morphogenesis. Study of the large-scale order produced by competitive dynamics promises to facilitate advances in basic evolutionary and developmental biology, as well as applied research in fields such as bioengineering and regenerative medicine that aim to regulate patterning outcomes.

Allometry, Scaling, and Ontogeny of Form-An Introduction to the Symposium.

Until recently, the study of allometry has been mostly descriptive, and consisted of a diversity of methods for fitting regressions to bivariate or multivariate morphometric data. During the past decade, researchers have been developing methods to extract biological information from allometric data that could be used to deduce the underlying mechanisms that gave rise to the allometry. In addition, an increasing effort has gone into understanding the kinetics of growth and the regulatory mechanisms that control growth of the body and its component parts. The study of allometry and scaling has now become an exceptionally diverse field, with different investigators applying state of the art methods and concepts in evolution, developmental biology, cell biology, and genetics. Diversity has caused divergence, and we felt that although there is general agreement about the new goals for the study of allometry (understanding underlying mechanisms and how those evolve to produce different morphologies), progress is hindered by lack of coordination among the different approaches. We felt the time was right to bring these diverse practitioners together in a symposium to discuss their most recent work in the hope of forging new functional, conceptual, and collaborative connections among established and novice practitioners.

Morphological Murals: The Scaling and Allometry of Butterfly Wing Patterns.

The color patterns of butterflies moths are exceptionally diverse, but are very stable within a species, so that most species can be identified on the basis of their color pattern alone. The color pattern is established in the wing imaginal disc during a prolonged period of growth and differentiation, beginning during the last larval instar and ending during the first few days of the pupal stage. During this period, a variety of diffusion and reaction-diffusion signaling mechanisms determine the positions and sizes of the various elements that make up the overall color pattern. The patterning occurs while the wing is growing from a small imaginal disc to a very large pupal wing. One would therefore expect that some or all aspects of the color pattern would be sensitive to the size of the developmental field on which pattern formation takes place. To study this possibility, we analyzed the color patterns of Junonia coenia from animals whose growth patterns were altered by periodic starvation during larval growth, which produced individuals with a large range of variation in body size and wing size. Analyses of the color patterns showed that the positions and size of the pattern elements scaled perfectly isometrically with wing size. This is a puzzling finding and suggests the operation of a homeostatic or robustness mechanism that stabilizes pattern in spite of variation in the growth rate and final size of the wing.

Exploring the Role of Insulin Signaling in Relative Growth: A Case Study on Wing-Body Scaling in Lepidoptera.

Adult forms emerge from the relative growth of the body and its parts. Each appendage and organ has a unique pattern of growth that influences the size and shape it attains. This produces adult size relationships referred to as static allometries, which have received a great amount of attention in evolutionary and developmental biology. However, many questions remain unanswered, for example: What sorts of developmental processes coordinate growth? And how do these processes change given variation in body size? It has become increasingly clear that nutrition is one of the strongest influences on size relationships. In insects, nutrition acts via insulin/TOR signaling to facilitate inter- and intra-specific variation in body size and appendage size. Yet, the mechanism by which insulin signaling influences the scaling of growth remains unclear. Here we will discuss the potential roles of insulin signaling in wing-body scaling in Lepidoptera. We analyzed the growth of wings in animals reared on different diet qualities that induce a range of body sizes not normally present in our laboratory populations. By growing wings in tissue culture, we survey how perturbation and stimulation of insulin/TOR signaling influences wing growth. To conclude, we will discuss the implications of our findings for the development and evolution of organismal form.

Wing morphogenesis in Lepidoptera.

The wings of Lepidoptera develop from imaginal disks that are made up of a simple two-layered epithelium whose structure is always congruent with the final adult wing. It is therefore possible to map every point on the imaginal disk to a location on the adult wing throughout the period of growth and morphogenesis. The wings of different species of Lepidoptera differ greatly in both size and shape, yet it is possible to fate-map homologous locations on the developing wing disks and explicitly monitor the growth, size, and shape of the wing, or any of its regions, throughout the entire ontogeny of the wing. The wing achieves its final form through spatially patterned cell divisions, oriented cell divisions, physical constraints on directional growth by an actin network between the wing veins, and by patterned cell death. Each of these factors contributes differently to morphogenesis and to the development of species-specific differences in wing shape. The final shape of the wing is sculpted out of the much larger imaginal disk by a pattern of programmed cell death that removes all cells distal to the bordering lacuna, and is responsible for the detailed outline of the wing.

The distinct roles of insulin signaling in polyphenic development.

Many insects have the ability to develop alternative morphologies in response to specific environmental signals such as photoperiod, temperature, nutrition and crowding. These signals are integrated by the brain and result in alternative patterns of secretion of developmental hormones like ecdysone, juvenile hormone and insulin-like growth factors, which, in turn, direct alternative developmental trajectories. Insulin signaling appears to be particularly important when the polyphenism involves differences in the sizes of the body, appendages and other structures, such as wings, mandibles and horns. Here we review recent advances in understanding the role of insulin signaling, and its interaction with other hormones, in the development of polyphenisms.

Unmodern Synthesis: Developmental Hierarchies and the Origin of Phenotypes.

The question of whether the modern evolutionary synthesis requires an extension has recently become a topic of discussion, and a source of controversy. We suggest that this debate is, for the most part, not about the modern synthesis at all. Rather, it is about the extent to which genetic mechanisms can be regarded as the primary determinants of phenotypic characters. The modern synthesis has been associated with the idea that phenotypes are the result of gene products, while supporters of the extended synthesis have suggested that environmental factors, along with processes such as epigenetic inheritance, and niche construction play an important role in character formation. We argue that the methodology of the modern evolutionary synthesis has been enormously successful, but does not provide an accurate characterization of the origin of phenotypes. For its part, the extended synthesis has yet to be transformed into a testable theory, and accordingly, has yielded few results. We conclude by suggesting that the origin of phenotypes can only be understood by integrating findings from all levels of the organismal hierarchy. In most cases, parts and processes from a single level fail to accurately explain the presence of a given phenotypic trait.

The Origin of Novelty Through the Evolution of Scaling Relationships.

Morphological novelty is often thought of as the evolution of an entirely new body plan or the addition of new structures to existing body plans. However, novel morphologies may also arise through modification of organ systems within an existing body plan. The evolution of novel scaling relationships between body size and organ size constitutes such a novel morphological feature. Experimental studies have demonstrated that there is genetic variation for allometries and that scaling relationships can evolve under artificial selection. We show that an allometry equation derived from Gompertz growth kinetics can accurately reconstruct complex non-linear allometries, and can be used to deduce the growth kinetics of the parts being compared. The equation also shows the relationship between ontogenetic and static allometries. We discuss how changes in the non-linear kinetics of growth can give rise to novel allometric relationships. Using parameters for wing and body growth of Manduca sexta, and a population simulation of the allometry equation, we show that selection on wing-body scaling can dramatically alter wing size without changing body size.