The control of body size in insects

Control mechanisms that regulate body size and tissue size have been sought at both the cellular and organismal level. Cell-level studies have revealed much about the control of cell growth and cell division, and how these processes are regulated by nutrition. Insulin signaling is the key mediator between nutrition and the growth of internal organs, such as imaginal disks, and is required for the normal proportional growth of the body and its various parts. The insulin-related peptides of insects do not appear to control growth by themselves, but act in conjunction with other hormones and signaling molecules, such as ecdysone and IDGFs. Size regulation cannot be understood solely on the basis of the mechanisms that control cell size and cell number. Size regulation requires mechanisms that gather information on a scale appropriate to the tissue or organ being regulated. A new model mechanism, using autocrine signaling, is outlined by which tissue and organ size regulation can be achieved. Body size regulation likewise requires a mechanism that integrates information at an appropriate scale. In insects, this mechanism operates by controlling the secretion of ecdysone, which is the signal that terminates the growth phase of development. The mechanisms for size assessment and the pathways by which they trigger ecdysone secretion are diverse and can be complex. The ways in which these higher-level regulatory mechanisms interact with cell- and molecular- level mechanisms are beginning to be elucidated.     

Explaining adaptive shifts in body size on islands: a life history approach

The tendency for island populations to differ in body size from their mainland relatives has been well documented, but the mechanisms for these size changes remain speculative. Explanations have typically been based on ecological interactions that directly favor either an increase or decrease in body size. While it is clear that direct ecological interactions can influence body size, life history shifts present an alternative explanation for observed insular size trends across phylogenetic groups and trophic levels. Here I describe how decreased resource availability and reduced predation pressure, the same selective forces invoked by previous hypotheses, can operate to produce body size changes via the evolution of life history traits. This mechanism is more generally applicable than previous explanations and is consistent with much of the available data.     

Obesity and colorectal cancer: epidemiology, mechanisms and candidate genes

There is increasing evidence that dysregulation of energy homeostasis is associated with colorectal carcinogenesis. Epidemiological data have consistently demonstrated a positive relation between increased body size and colorectal malignancy, whereas mechanistic studies have sought to uncover obesity-related carcinogenic pathways. The phenomenon of "insulin resistance" or the impaired ability to normalize plasma glucose levels has formed the core of these pathways, but other mechanisms have also been advanced. Obesity-induced insulin resistance leads to elevated levels of plasma insulin, glucose and fatty acids. Exposure of the colonocyte to heightened concentrations of insulin may induce a mitogenic effect within these cells, whereas exposure to glucose and fatty acids may induce metabolic perturbations, alterations in cell signaling pathways and oxidative stress. The importance of chronic inflammation in the pathogenesis of obesity has recently been highlighted and may represent an additional mechanism linking increased adiposity to colorectal carcinogenesis. This review provides an overview of the epidemiology of body size and colorectal neoplasia and outlines current knowledge of putative mechanisms advanced to explain this relation. Family based studies have shown that the propensity to become obese is heritable, but this is only manifest in conditions of excess energy intake over expenditure. Inheritance of a genetic profile that predisposes to increased body size may also be predictive of colorectal cancer. Genomewide scans, linkage studies and candidate gene investigations have highlighted more than 400 chromosomal regions that may harbor variants that predispose to increased body size. The genetics underlying the pathogenesis of obesity are likely to be complex, but variants in a range of different genes have already been associated with increased body size and insulin resistance. These include genes encoding elements of insulin signaling, adipocyte metabolism and differentiation, and regulation of energy expenditure. A number of investigators have begun to study genetic variants within these pathways in relation to colorectal neoplasia, but at present data remain limited to a handful of studies. These pathways will be discussed with particular reference to genetic polymorphisms that have been associated with obesity and insulin resistance.     

The evolution of large‐scale body size clines in Plethodon salamanders: evidence of heat‐balance or species‐specific artifact?

A major goal in macroecology is to determine how body size varies geographically, and explain why such patterns exist. Recently, a grid‐cell assemblage analysis found significant body size trends with latitude and temperature in Plethodon salamanders, and support for the heat‐balance hypothesis as a possible explanation for these trends. Here we demonstrate that the heat‐balance hypothesis is unlikely to have generated this pattern, and that there is no overall body size trend with temperature in Plethodon. Using data from 3155 local Plethodon assemblages, we find no support for body size clines with latitude, and no relationship between body size and temperature. We also found that body size did not covary with elevation, in contrast to what was predicted by heat‐balance. We then examined the various scenarios under which body size clines across grid‐cell assemblages could evolve via heat‐balance, and found that none were tenable in light of the existing data. Instead, a single, widely distributed species was responsible for the pattern across grid‐cell assemblages. Finally, we examined why phylogenetic eigenvector regression does not account for phylogenetic non‐independence among taxa, and should not be used to account for shared evolutionary history in assembly‐level analyses. Assemblage‐level patterns are a useful means of assessing biogeographic trends, and are an important complement to within‐species and cross‐species patterns. However, while the use of grid‐cell assemblage approaches from digital databases is expedient, their results must be examined critically, and whenever possible, compared with data obtained from local species assemblages (particularly for ecological mechanisms that operate at the level of individuals). Finally, our results emphasize the importance of using corroborative data to evaluate alternative hypotheses, so that potential mechanisms that explain bioegeographic patterns are properly assigned.     

Genetic control of size in Drosophila

During the past ten years, significant progress has been made in understanding the basic mechanisms of the development of multicellular organisms. Genetic analysis of the development of Caenorhabditis elegans and Drosophila has unearthed a fruitful number of genes involved in establishing the basic body plan, patterning of limbs, specification of cell fate and regulation of programmed cell death. The genes involved in these developmental processes have been conserved throughout evolution and homologous genes are involved in the patterning of insect and human limbs. Despite these important discoveries, we have learned astonishingly little about one of the most obvious distinctions between animals: their difference in body size. The mass of the smallest mammal, the bumble-bee bat, is 2 g while that of the largest mammal, the blue whale, is 150 t or 150 million grams. Remarkably, even though they are in the same class, body size can vary up to 75-million-fold. Furthermore, this body growth can be finite in the case of most vertebrates or it can occur continuously throughout life, as for trees, molluscs and large crustaceans. Currently, we know comparatively little about the genetic control of body size. In this article we will review recent evidence from vertebrates and particularly from Drosophila that implicates insulin/insulin-like growth factor-I and other growth pathways in the control of cell, organ and body size.     

Cell size is positively correlated between different tissues in passerine birds and amphibians,but not necessarily in mammals

We examined cell size correlations between tissues, and cell size to body mass relationships in passerine birds, amphibians and mammals. The size correlated highly between all cell types in birds and amphibians; mammalian tissues clustered by size correlation in three tissue groups. Erythrocyte size correlated well with the volume of other cell types in birds and amphibians, but poorly in mammals. In birds, body mass correlated positively with the size of all cell types including erythrocytes, and in mammals only with the sizes of some cell types. Size of mammalian erythrocytes correlated with body mass only within the most taxonomically uniform group of species (rodents and lagomorphs). Cell volume increased with body mass of birds and mammals to less than 0.3 power, indicating that body size evolved mostly by changes in cell number. Our evidence suggests that epigenetic mechanisms determining cell size relationships in tissues are conservative in birds and amphibians, but less stringent in mammals. The patterns of cell size to body mass relationships we obtained challenge some key assumptions of fractal and cellular models used by allometric theory to explain mass-scaling of metabolism. We suggest that the assumptions in both models are not universal, and that such models need reformulation.     

Body size determination in insects: a review and synthesis of size‐ and brain‐dependent and independent mechanisms

Body size determination requires a mechanism for sensing size and a mechanism for linking size information to the termination of growth. Although the hormonal mechanisms that terminate growth are well elucidated, the mechanisms by which a body senses its own size are only partially understood; most of this understanding has come from the study of the mechanisms that control insect moulting and metamorphosis. We first review and discuss advances in our understanding of the physiological mechanisms by which insect larvae sense their size. Second, we present new findings on how larvae in which the size‐sensing mechanism has been disrupted eventually terminate growth (in a size‐independent manner). We synthesize recent insights into the genetic and molecular mechanisms of ecdysteroid regulation in Drosophila melanogaster with developmental physiology findings in Manduca sexta, paving the way for an integrated understanding of the mechanisms of body size regulation.     

Discoidin domain receptor 2 (DDR2) regulates body size and fat metabolism in mice

Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is activated by fibrillar collagens, which act as its endogenous ligand. DDR2 regulates cell proliferation, cell adhesion, migration, extracellular matrix remodeling and reproductive functions. Both DDR2 null allele mice and mice with a recessive, loss-of-function allele for Ddr2 exhibit dwarfing and a reduction in body weight. However, the detailed mechanisms by which DDR2 exerts its positive systemic regulation of whole body size, local skeletal size and fat tissue volume remain to be clarified. To investigate the systemic role of DDR2 in body size regulation, we produced transgenic mice in which the DDR2 protein is overexpressed, then screened the transgenic mice for abnormalities using systematic mouse abnormality screening. The modified-SHIPRA screen revealed that only the parameter of body size was significantly different among the genotypes. We also discovered that the body length was significantly increased, while the body weight was significantly decreased in transgenic mice compared to their littermate controls. We also found that the epididymal fat pads were significantly decreased in transgenic mice compared to normal littermate mice, which may have been the cause of the leptin decrement in the transgenic mice. The new insight that DDR2 might promote metabolism in adipocyte cells is very interesting, but more experiments will be needed to elucidate the direct relation between DDR2 and adipose-derived hormones. Taken together, our data demonstrated that DDR2 might play a systemic role in the regulation of body size thorough skeletal formation and fat metabolism.     

A Quantitative Analysis of Growth and Size Regulation in Manduca sexta: The Physiological Basis of Variation in Size and Age at Metamorphosis

Body size and development time are important life history traits because they are often highly correlated with fitness. Although the developmental mechanisms that control growth have been well studied, the mechanisms that control how a species-characteristic body size is achieved remain poorly understood. In insects adult body size is determined by the number of larval molts, the size increment at each molt, and the mechanism that determines during which instar larval growth will stop. Adult insects do not grow, so the size at which a larva stops growing determines adult body size. Here we develop a quantitative understanding of the kinetics of growth throughout larval life of Manduca sexta, under different conditions of nutrition and temperature, and for genetic strains with different adult body sizes. We show that the generally accepted view that the size increment at each molt is constant (Dyar’s Rule) is systematically violated: there is actually a progressive increase in the size increment from instar to instar that is independent of temperature. In addition, the mass-specific growth rate declines throughout the growth phase in a temperature-dependent manner. We show that growth within an instar follows a truncated Gompertz trajectory. The critical weight, which determines when in an instar a molt will occur, and the threshold size, which determines which instar is the last, are different in genetic strains with different adult body sizes. Under nutrient and temperature stress Manduca has a variable number of larval instars and we show that this is due to the fact that more molts at smaller increments are taken before threshold size is reached. We test whether the new insight into the kinetics of growth and size determination are sufficient to explain body size and development time through a mathematical model that incorporates our quantitative findings.     

Life history evolution and cellular mechanisms associated with increased size in high‐altitude Drosophila

Understanding the physiological and genetic basis of growth and body size variation has wide‐ranging implications, from cancer and metabolic disease to the genetics of complex traits. We examined the evolution of body and wing size in high‐altitude Drosophila melanogaster from Ethiopia, flies with larger size than any previously known population. Specifically, we sought to identify life history characteristics and cellular mechanisms that may have facilitated size evolution. We found that the large‐bodied Ethiopian flies laid significantly fewer but larger eggs relative to lowland, smaller‐bodied Zambian flies. The highland flies were found to achieve larger size in a similar developmental period, potentially aided by a reproductive strategy favoring greater provisioning of fewer offspring. At the cellular level, cell proliferation was a strong contributor to wing size evolution, but both thorax and wing size increases involved important changes in cell size. Nuclear size measurements were consistent with elevated somatic ploidy as an important mechanism of body size evolution. We discuss the significance of these results for the genetic basis of evolutionary changes in body and wing size in Ethiopian D. melanogaster.     

Bergmann's Principle and Deep-Water Gigantism in Marine Crustaceans

We present a review of the Bergmann's principle and deep-water gigantism in marine crustaceans. An increase in the geographic latitude and depth of crustaceans habitat (correlating mainly with lower temperatures) leads to an increased cell size, life span of the animal, and, as a result, an increase in the body size. Since Bergmann's principle and deep-water gigantism appear to be based on the same biological mechanisms, we propose a unified principle, according to which the size of the crustacean's body increases along the temperature gradient.     

Animal body size distributions: patterns, mechanisms and implications

Documenting the shape of the frequency distribution of species body sizes for an animal taxon appears at first sight a straightforward task. However, a variety of patterns has been reported, and a consensus is only now being reached through an understanding of how potential biases may affect observed shapes of distributions. A new body of evidence suggests that, at large scales, size distributions are right-skewed, even on logarithmic axes. If body size distributions can be described with certainty, this will allow assessment of the mechanisms proposed to generate them, and will be an important step towards understanding the structure and dynamics of animal assemblages.     

Genetic variance in temperature dependent adult size deriving from physiological genetic variation at temperature boundaries

An increase in genetic variation in body size has often been observed under stress; an increase in dominance variance and interaction variance as well as in additive genetic variance has been reported. The increase in genetic variation must be caused by physiological mechanisms that are specific to adverse environments. A model is proposed to explain the occurrence of an increase in genetic variation in body size in Drosophila at extreme temperatures. The model has parameters specific to the low- and high-temperature regions of the viable range. Additive genetic variation in the boundary temperatures leads to a marked increase in additive genetic variation in development rate and body size at extreme temperatures. Additive genetic variation in the temperature sensitivity in the low- and high-temperature regions adds non-additive genetic variation. Development rate shows patterns in additive genetic variation that differ from the patterns of genetic variation in body size; therefore, the genetic correlation between development rate and body size changes sign repeatedly as a function of temperature. The existence of dominance in the genetic variation in the boundary temperatures or in the low- and high-temperature sensitivities leads to a higher total genetic variance due to higher dominance and interaction variance, for both development rate and body size. This revised version was published online in July 2006 with corrections to the Cover Date.     

Interactions among mechanisms of sexual selection on male body size and head shape in a sexually dimorphic fly

Abstract Darwin envisaged male-male and male-female interactions as mutually supporting mechanisms of sexual selection, in which the best armed males were also the most attractive to females. Although this belief continues to predominate today, it has been challenged by sexual conflict theory, which suggests that divergence in the interests of males and females may result in conflicting sexual selection. This raises the empirical question of how multiple mechanisms of sexual selection interact to shape targeted traits. We investigated sexual selection on male morphology in the sexually dimorphic fly Prochyliza xanthostoma , using indices of male performance in male-male and male-female interactions in laboratory arenas to calculate gradients of direct, linear selection on male body size and an index of head elongation. In male-male combat, the first interaction with a new opponent selected for large body size but reduced head elongation, whereas multiple interactions with the same opponent favored large body size only. In male-female interactions, females preferred males with relatively elongated heads, but male performance of the precopulatory leap favored large body size and, possibly, reduced head elongation. In addition, the amount of sperm transferred (much of which is ingested by females) was an increasing function of both body size and head elongation. Thus, whereas both male-male and male-female interactions favored large male body size, male head shape appeared to be subject to conflicting sexual selection. We argue that conflicting sexual selection may be a common result of divergence in the interests of the sexes.     

What is slow axonal transport?

While the phenomenon of slow axonal transport is widely agreed upon, its underlying mechanism has been controversial for decades. There is now persuasive evidence that several different mechanisms could contribute to slow axonal transport. Yet proponents of different theories have been hesitant to explicitly integrate what were, at least initially, opposing models. We suggest that slow transport is a multivariate phenomenon that arises through mechanisms that minimally include: molecular motor-based transport of polymers and soluble proteins as multi-protein complexes; diffusion; and en bloc transport of the axonal framework by low velocity transport and towed growth (due to increases in body size). In addition to integrating previously described mechanisms of transport, we further suggest that only a subset of transport modes operate in a given neuron depending on the region, length, species, cell type, and developmental stage. We believe that this multivariate approach to slow axonal transport better explains its complex phenomenology: including its bi-directionality; the differing velocities of transport depending on cargo, as well differing velocities due to anatomy, cell type and developmental stage.     

Body size distributions of large Costa Rican dry forest moths and the underlying relationship between plant and pollinator morphology

There has been much recent interest in explaining patterns of body size variation within species assemblages. One observation is that frequency distributions of species' body size commonly exhibit a right-skew, even on a logarithmic scale. Here we examine the species' body size distributions in two assemblages of large Costa Rican moths. We find that neither adult Sphingidae or Saturniidae exhibit the classic log right-skewed pattern. Furthermore, the species' body size distributions in these two groups are markedly different, which we suggest is a result of differential selective pressures related to resource and mate acquisition. For Sphingidae, we show (1) that body size is positively correlated with tongue length, and (2) that the distribution of sphingid body sizes/tongue lengths closely matches the distribution of flower corolla tube depths in sphingid-pollinated plants. Thus, morphological fitting between plants and pollinators seems to underlie the species' body size distribution of this sphingid assemblage. We discuss the significance of these results in the context of current theory on mechanisms driving species' body size distributions. Finally, we present an evolutionary hypothesis for the diversity of body sizes seen in this sphingid assemblage related to reciprocal interactions between plants and pollinators. This hypothesis can be tested within a rigorous phylogenetic framework, although a systematic phylogenetic analysis of Neotropical Sphingidae does not currently exist.     

Controlling the size of organs and organisms

A key difference between yeast and metazoans is the need of the latter to regulate cell proliferation and growth to create organs (and organisms) of reproducible size and shape. Great progress has been made in understanding how growth, cell size and the cell cycle are controlled in metazoans. Recent work has shown that disruption of conserved components of the insulin and Tor kinase pathways can alter organ size, indicating that the normal functioning of these pathways is essential for organ size control. However, disruption of genes that regulate patterning and of genes that control cell adhesion and cell polarity has a much more dramatic effect on final organ size than does manipulation of the cell cycle or of basal growth control mechanisms. These data point to an 'organ-size checkpoint' that regulates cell division, cell growth and apoptosis. Recent data suggests that cell competition may play an important role in implementing the organ-size checkpoint.     

Critical weight in the development of insect body size

Body size is one of the most important life history characters of organisms, yet little is known of the physiological mechanisms that regulate either body size or variation in body size. Here, we examined one of these mechanisms, the critical weight, which is defined as the minimal mass at which further growth is not necessary for a normal time course to pupation. The critical weight occurred at 55% of peak larval mass in laboratory-reared larvae of the tobacco hornworm Manduca sexta. We examined the effects of genetic and environmental variation in the critical weight on body size. As in many other insects, Manduca larvae reared on poor diets were smaller and those reared at lower temperatures were larger than control animals. We demonstrated that the critical weight was lower on low quality diets but did not change with temperature. There was significant genetic variation for body size, for plasticity of body size, and for critical weight, but not for plasticity of critical weight. Variation in the critical weight accounted for 73% of between-family variance in peak larval size, whereas plasticity of critical weight was not significantly correlated with plasticity of body size. Our results suggest that although critical weight is an important factor in determining body size and enabling the evolution of body size, it may, at the same time, act as a constraint on the evolution of plasticity of body size. Thus, the determinants of body size and the determinants of plasticity of body size do not need to be identical.     

The control of cell number during central nervous system development in flies and mice

Growth is confined within a size that is normal for each species, revealing that somehow an organism 'knows' when this size has been reached. Within a species, growth is also variable, but despite this, proportion and structure are maintained. Perhaps, the key element in the control of size is the control of cell number. Here we review current knowledge on the mechanisms controlling cell number in the nervous system of vertebrates and flies. During growth, clonal expansion is confined, the number of progeny cells is balanced through the control of cell survival and cell proliferation and excess cells are eliminated by apoptosis. Simultaneously, organ architecture emerges and as neurons become active they also influence growth. The interactive control of cell number provides developmental plasticity to nervous system development. Many findings are common between flies and mice, other aspects have been studied more in one organism than the other and there are also aspects that are unique to either organism. Although cell number control has long been studied in the nervous system, analogous mechanisms are likely to operate during the growth of other organs and organisms.     

The developmental and physiological basis of body size evolution in an insect

The evolution of body size is a dominant feature of animal evolution. However, little is known about how the underlying developmental mechanisms that determine size change as body size evolves. Here we report on a case of body size evolution in the tobacco hornworm Manduca sexta that occurred over a period of nearly 30 years. We take advantage of an extensive series of physiological studies performed in the early 1970s that established the parameters that regulate body size in this species and compare their values with those of modern individuals that are descendants of the same colony. We show that three of the five processes that determine adult body size changed during this period, while two remained constant. Changes in these three developmental processes completely account for the observed evolutionary change in body size.