Showing papers on "Developmental plasticity published in 2020"

Regenerative lineages and immune-mediated pruning in lung cancer metastasis

Abstract: Developmental processes underlying normal tissue regeneration have been implicated in cancer, but the degree of their enactment during tumor progression and under the selective pressures of immune surveillance, remain unknown. Here we show that human primary lung adenocarcinomas are characterized by the emergence of regenerative cell types, typically seen in response to lung injury, and by striking infidelity among transcription factors specifying most alveolar and bronchial epithelial lineages. In contrast, metastases are enriched for key endoderm and lung-specifying transcription factors, SOX2 and SOX9, and recapitulate more primitive transcriptional programs spanning stem-like to regenerative pulmonary epithelial progenitor states. This developmental continuum mirrors the progressive stages of spontaneous outbreak from metastatic dormancy in a mouse model and exhibits SOX9-dependent resistance to natural killer cells. Loss of developmental stage-specific constraint in macrometastases triggered by natural killer cell depletion suggests a dynamic interplay between developmental plasticity and immune-mediated pruning during metastasis. Single-cell analysis of lung cancer progression uncovers developmental and regenerative programs co-opted by cancer cells and immune-mediated pruning during metastatic outbreak

Metabolism and growth adaptation to environmental conditions in Drosophila.

Abstract: Organisms adapt to changing environments by adjusting their development, metabolism, and behavior to improve their chances of survival and reproduction. To achieve such flexibility, organisms must be able to sense and respond to changes in external environmental conditions and their internal state. Metabolic adaptation in response to altered nutrient availability is key to maintaining energy homeostasis and sustaining developmental growth. Furthermore, environmental variables exert major influences on growth and final adult body size in animals. This developmental plasticity depends on adaptive responses to internal state and external cues that are essential for developmental processes. Genetic studies have shown that the fruit fly Drosophila, similarly to mammals, regulates its metabolism, growth, and behavior in response to the environment through several key hormones including insulin, peptides with glucagon-like function, and steroid hormones. Here we review emerging evidence showing that various environmental cues and internal conditions are sensed in different organs that, via inter-organ communication, relay information to neuroendocrine centers that control insulin and steroid signaling. This review focuses on endocrine regulation of development, metabolism, and behavior in Drosophila, highlighting recent advances in the role of the neuroendocrine system as a signaling hub that integrates environmental inputs and drives adaptive responses.

Developmental plasticity and evolutionary explanations.

Abstract: Developmental plasticity looks like a promising bridge between ecological and developmental perspectives on evolution. Yet, there is no consensus on whether plasticity is part of the explanation for adaptive evolution or an optional "add-on" to genes and natural selection. Here, we suggest that these differences in opinion are caused by differences in the simplifying assumptions, and particular idealizations, that enable evolutionary explanation. We outline why idealizations designed to explain evolution through natural selection prevent an understanding of the role of development, and vice versa. We show that representing plasticity as a reaction norm conforms with the idealizations of selective explanations, which can give the false impression that plasticity has no explanatory power for adaptive evolution. Finally, we use examples to illustrate why evolutionary explanations that include developmental plasticity may in fact be more satisfactory than explanations that solely refer to genes and natural selection.

Developmental programming of mitochondrial biology: a conceptual framework and review.

Abstract: Research on mechanisms underlying the phenomenon of developmental programming of health and disease has focused primarily on processes that are specific to cell types, organs and phenotypes of interest. However, the observation that exposure to suboptimal or adverse developmental conditions concomitantly influences a broad range of phenotypes suggests that these exposures may additionally exert effects through cellular mechanisms that are common, or shared, across these different cell and tissue types. It is in this context that we focus on cellular bioenergetics and propose that mitochondria, bioenergetic and signalling organelles, may represent a key cellular target underlying developmental programming. In this review, we discuss empirical findings in animals and humans that suggest that key structural and functional features of mitochondrial biology exhibit developmental plasticity, and are influenced by the same physiological pathways that are implicated in susceptibility for complex, common age-related disorders, and that these targets of mitochondrial developmental programming exhibit long-term temporal stability. We conclude by articulating current knowledge gaps and propose future research directions to bridge these gaps.

Phenotypic Switching Resulting From Developmental Plasticity: Fixed or Reversible?

Abstract: The prevalent view of developmental phenotypic switching holds that phenotype modifications occurring during critical windows of development are "irreversible" - that is, once produced by environmental perturbation, the consequent juvenile and/or adult phenotypes are indelibly modified. Certainly, many such changes appear to be non-reversible later in life. Yet, whether animals with switched phenotypes during early development are unable to return to a normal range of adult phenotypes, or whether they do not experience the specific environmental conditions necessary for them to switch back to the normal range of adult phenotypes, remains an open question. Moreover, developmental critical windows are typically brief, early periods punctuating a much longer period of overall development. This leaves open additional developmental time for reversal (correction) of a switched phenotype resulting from an adverse environment early in development. Such reversal could occur from right after the critical window "closes," all the way into adulthood. In fact, examples abound of the capacity to return to normal adult phenotypes following phenotypic changes enabled by earlier developmental plasticity. Such examples include cold tolerance in the fruit fly, developmental switching of mouth formation in a nematode, organization of the spinal cord of larval zebrafish, camouflage pigmentation formation in larval newts, respiratory chemosensitivity in frogs, temperature-metabolism relations in turtles, development of vascular smooth muscle and kidney tissue in mammals, hatching/birth weight in numerous vertebrates,. More extreme cases of actual reversal (not just correction) occur in invertebrates (e.g., hydrozoans, barnacles) that actually 'backtrack' along normal developmental trajectories from adults back to earlier developmental stages. While developmental phenotypic switching is often viewed as a permanent deviation from the normal range of developmental plans, the concept of developmental phenotypic switching should be expanded to include sufficient plasticity allowing subsequent correction resulting in the normal adult phenotype.

TNF-Mediated Homeostatic Synaptic Plasticity: From in vitro to in vivo Models.

Abstract: Since it was first described almost 30 years ago, homeostatic synaptic plasticity (HSP) has been hypothesized to play a key role in maintaining neuronal circuit function in both developing and adult animals. While well characterized in vitro, determining the in vivo roles of this form of plasticity remains challenging. Since the discovery that the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) mediates some forms of HSP, it has been possible to probe some of the in vivo contribution of TNF-mediated HSP. Work from our lab and others has found roles for TNF-HSP in a variety of functions, including the developmental plasticity of sensory systems, models of drug addiction, and the response to psychiatric drugs.

Shifting Developmental Trajectories During Critical Periods of Brain Formation

Abstract: Critical periods of brain development are epochs of heightened plasticity driven by environmental influence necessary for normal brain function. Recent studies are beginning to shed light on the possibility that timely interventions during critical periods hold potential to reorient abnormal developmental trajectories in animal models of neurological and neuropsychiatric disorders. In this review, we re-examine the criteria defining critical periods, highlighting the recently discovered mechanisms of developmental plasticity in health and disease. In addition, we touch upon technological improvements for modeling critical periods in human-derived neural networks in vitro. These scientific advances associated with the use of developmental manipulations in the immature brain of animal models are the basic preclinical systems that will allow the future translatability of timely interventions into clinical applications for neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD) and schizophrenia.

Thermal Plasticity in Insects’ Response to Climate Change and to Multifactorial Environments

Abstract: Phenotypic plasticity, the property by which living organisms express different phenotypes depending on environmental conditions, can impact their response to environmental perturbation, including that resulting from climate change When exposed to altered environmental conditions, phenotypic plasticity might help or might hinder both immediate survival and future adaptation Because climate change will cause more than a global rise in mean temperatures, it is valuable to consider the combined effects of temperature and other environmental variables on trait expression (thermal plasticity), as well as trait evolution (thermal adaptation) In this review, we focus primarily on thermal developmental plasticity in insects We discuss the genomics of thermal plasticity and its relationship to thermal adaptation and thermal tolerance, and to climate change and multifactorial environments

Experience-dependent plasticity in an innate social behavior is mediated by hypothalamic LTP.

Abstract: All animals can perform certain survival behaviors without prior experience, suggesting a "hard wiring" of underlying neural circuits. Experience, however, can alter the expression of innate behaviors. Where in the brain and how such plasticity occurs remains largely unknown. Previous studies have established the phenomenon of "aggression training," in which the repeated experience of winning successive aggressive encounters across multiple days leads to increased aggressiveness. Here, we show that this procedure also leads to long-term potentiation (LTP) at an excitatory synapse, derived from the posteromedial part of the amygdalohippocampal area (AHiPM), onto estrogen receptor 1-expressing (Esr1+) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl). We demonstrate further that the optogenetic induction of such LTP in vivo facilitates, while optogenetic long-term depression (LTD) diminishes, the behavioral effect of aggression training, implying a causal role for potentiation at AHiPM→VMHvlEsr1 synapses in mediating the effect of this training. Interestingly, ∼25% of inbred C57BL/6 mice fail to respond to aggression training. We show that these individual differences are correlated both with lower levels of testosterone, relative to mice that respond to such training, and with a failure to exhibit LTP after aggression training. Administration of exogenous testosterone to such nonaggressive mice restores both behavioral and physiological plasticity. Together, these findings reveal that LTP at a hypothalamic circuit node mediates a form of experience-dependent plasticity in an innate social behavior, and a potential hormone-dependent basis for individual differences in such plasticity among genetically identical mice.

Embryonic Temperature Programs Phenotype in Reptiles

Abstract: Reptiles are critically affected by temperature throughout their lifespan, but especially so during early development. Temperature-induced changes in phenotype are a specific example of a broader phenomenon called phenotypic plasticity in which a single individual is able to develop different phenotypes when exposed to different environments. With climate change occurring at an unprecedented rate, it is important to study temperature effects on reptiles. For example, the potential impact of global warming is especially pronounced in species with temperature-dependent sex determination (TSD) because temperature has a direct effect on a key phenotypic (sex) and demographic (population sex ratios) trait. Reptiles with TSD also serve as models for studying temperature effects on the development of other traits that display continuous variation. Temperature directly influences metabolic and developmental rate of embryos and can have permanent effects on phenotype that last beyond the embryonic period. For instance, incubation temperature programs post-hatching hormone production and growth physiology, which can profoundly influence fitness. Here, we review current knowledge of temperature effects on phenotypic and developmental plasticity in reptiles. First, we examine the direct effect of temperature on biophysical processes, the concept of thermal performance curves, and the process of thermal acclimation. After discussing these reversible temperature effects, we focus the bulk of the review on developmental programming of phenotype by temperature during embryogenesis (i.e., permanent developmental effects). We focus on oviparous species because eggs are especially susceptible to changes in ambient temperature. We then discuss recent work probing the role of epigenetic mechanisms in mediating temperature effects on phenotype. Based on phenotypic effects of temperature, we return to the potential impact of global warming on reptiles. Finally, we highlight key areas for future research, including the identification of temperature sensors and assessment of genetic variation for thermosensitivity.

Conserved nuclear hormone receptors controlling a novel plastic trait target fast-evolving genes expressed in a single cell.

Abstract: Environment shapes development through a phenomenon called developmental plasticity. Deciphering its genetic basis has potential to shed light on the origin of novel traits and adaptation to environmental change. However, molecular studies are scarce, and little is known about molecular mechanisms associated with plasticity. We investigated the gene regulatory network controlling predatory vs. non-predatory dimorphism in the nematode Pristionchus pacificus and found that it consists of genes of extremely different age classes. We isolated mutants in the conserved nuclear hormone receptor nhr-1 with previously unseen phenotypic effects. They disrupt mouth-form determination and result in animals combining features of both wild-type morphs. In contrast, mutants in another conserved nuclear hormone receptor nhr-40 display altered morph ratios, but no intermediate morphology. Despite divergent modes of control, NHR-1 and NHR-40 share transcriptional targets, which encode extracellular proteins that have no orthologs in Caenorhabditis elegans and result from lineage-specific expansions. An array of transcriptional reporters revealed co-expression of all tested targets in the same pharyngeal gland cell. Major morphological changes in this gland cell accompanied the evolution of teeth and predation, linking rapid gene turnover with morphological innovations. Thus, the origin of feeding plasticity involved novelty at the level of genes, cells and behavior.

Developmental Plasticity Shapes Social Traits and Selection in a Facultatively Eusocial Bee

Abstract: Developmental plasticity generates phenotypic variation, but how it contributes to evolutionary change is unclear. Phenotypes of individuals in caste-based (eusocial) societies are particularly sensitive to developmental processes, and the evolutionary origins of eusociality may be rooted in developmental plasticity of ancestral forms. We used an integrative genomics approach to evaluate the relationships among developmental plasticity, molecular evolution, and social behavior in a bee species (Megalopta genalis) that expresses flexible sociality, and thus provides a window into the factors that may have been important at the evolutionary origins of eusociality. We find that differences in social behavior are derived from genes that also regulate sex differentiation and metamorphosis. Positive selection on social traits is influenced by the function of these genes in development. We further identify evidence that social polyphenisms may become encoded in the genome via genetic changes in regulatory regions, specifically in transcription factor binding sites. Taken together, our results provide evidence that developmental plasticity provides the substrate for evolutionary novelty and shapes the selective landscape for molecular evolution in a major evolutionary innovation: Eusociality.

Thermal Plasticity of the Kelp Laminaria digitata (Phaeophyceae) Across Life Cycle Stages Reveals the Importance of Cold Seasons for Marine Forests

Abstract: Phenotypic plasticity (genotype x environment interaction) is an especially important means for sessile organisms to cope with environmental variation. While kelps, the globally most productive group of seaweeds, generally possess a wide thermal performance range, kelp populations at their warm distribution limits are threatened by ocean warming. Here, we investigated effects of temperature during ontogeny of the kelp Laminaria digitata across haploid gametophyte and diploid sporophyte life cycle stages in five distinct genetic lines. We hypothesized that thermal plasticity increases trait performance of juvenile sporophytes in experimental temperatures that match the temperature experienced during gametogenesis and recruitment, and that plasticity differs among genetic lines (genetic variation for plasticity). We applied a full-factorial experimental design to generate different temperature histories by applying 5°C and 15°C during meiospore germination, gametogenesis of parental gametophytes and recruitment of offspring sporophytes (19–26 days), and juvenile sporophyte rearing (91–122 days). We then tested for thermal plasticity among temperature history treatments at 5°C and 15°C in a final 12-day experiment assessing growth, the storage compound mannitol, carbon and nitrogen contents, and fluorometric responses in 3–4 month old sporophytes for five genetic lines. Our study provides evidence for the importance of cold temperatures at early development on later sporophyte performance of L. digitata. Gametogenesis and recruitment at 5°C promoted higher growth of offspring sporophytes across experimental temperatures. While photosynthetic capacity was higher at 15°C, carbon and nitrogen storage were higher at 5°C, both showing fast acclimation responses. We identified an important role of genetic variation for plasticity in shaping L. digitata’s thermal plasticity. Trait performance at 5°C or 15°C (reaction norm slopes) differed among genetic lines, even showing opposite response patterns. Interestingly, genetic variation for plasticity was only significant when sporophytes were reared at 5°C. Thus, we provide evidence that the cold-temperate to Arctic kelp species, L. digitata, which possesses a wide temperature tolerance between 0°C and 23°C, is impaired by warm temperature during gametogenesis and recruitment, reducing growth of juvenile sporophytes and expression of variable thermal plasticity in the wild.

The influence of developmental diet on reproduction and metabolism in Drosophila.

Abstract: The adaptive significance of phenotypic changes elicited by environmental conditions experienced early in life has long attracted attention in evolutionary biology. In this study, we used Drosophila melanogaster to test whether the developmental diet produces phenotypes better adapted to cope with similar nutritional conditions later in life. To discriminate among competing hypotheses on the underlying nature of developmental plasticity, we employed a full factorial design with several developmental and adult diets. Specifically, we examined the effects of early- and late-life diets (by varying their yeast and sugar contents) on reproductive fitness and on the amount of energy reserves (fat and glycogen) in two wild-caught populations. We found that individuals that had developed on either low-yeast or high-sugar diet showed decreased reproductive performance regardless of their adult nutritional environment. The lower reproductive fitness might be caused by smaller body size and reduced ovariole number. Overall, these results are consistent with the silver spoon concept, which posits that development in a suboptimal environment negatively affects fitness-associated traits. On the other hand, the higher amount of energy reserves (fat) in individuals that had developed in a suboptimal environment might represent either an adaptive response or a side-effect of compensatory feeding. Our findings suggest that the observed differences in the adult physiology induced by early-life diet likely result from inevitable and general effects of nutrition on the development of reproductive and metabolic organs, rather than from adaptive mechanisms.

Stability in the Face of Change: Lifelong Experience-Dependent Plasticity in the Sensory Cortex.

Abstract: Plasticity is a fundamental property of the nervous system that enables its adaptations to the ever-changing environment. Heightened plasticity typical for developing circuits facilitates their robust experience-dependent functional maturation. This plasticity wanes during adolescence to permit the stabilization of mature brain function, but abundant evidence supports that adult circuits exhibit both transient and long-term experience-induced plasticity. Cortical plasticity has been extensively studied throughout the life span in sensory systems and the main distinction between development and adulthood arising from these studies is the concept that passive exposure to relevant information is sufficient to drive robust plasticity early in life, while higher-order attentional mechanisms are necessary to drive plastic changes in adults. Recent work in the primary visual and auditory cortices began to define the circuit mechanisms that govern these processes and enable continuous adaptation to the environment, with transient circuit disinhibition emerging as a common prerequisite for both developmental and adult plasticity. Drawing from studies in visual and auditory systems, this review article summarizes recent reports on the circuit and cellular mechanisms of experience-driven plasticity in the developing and adult brains and emphasizes the similarities and differences between them. The benefits of distinct plasticity mechanisms used at different ages are discussed in the context of sensory learning, as well as their relationship to maladaptive plasticity and neurodevelopmental brain disorders. Knowledge gaps and avenues for future work are highlighted, and these will hopefully motivate future research in these areas, particularly those about the learning of complex skills during development.

Expression profiling of winged- and wingless-destined pea aphid embryos implicates insulin/insulin growth factor signaling in morph differences.

Abstract: Developmental plasticity allows the matching of adult phenotypes to different environments. Although considerable effort has gone into understanding the evolution and ecology of plasticity, less is known about its developmental genetic basis. We focused on the pea aphid wing polyphenism, in which high- or low-density environments cause viviparous aphid mothers to produce winged or wingless offspring, respectively. Maternally provided ecdysone signals to embryos to be winged or wingless, but it is unknown how embryos respond to that signal. We used transcriptional profiling to investigate the gene expression state of winged-destined (WD) and wingless-destined (WLD) embryos at two developmental stages. We found that embryos differed in a small number of genes, and that gene sets were enriched for the insulin-signaling portion of the FoxO pathway. To look for a global signature of insulin signaling, we examined the size and stage of WD and WLD embryos but found no differences. These data suggest the hypothesis that FoxO signaling is important for morph development in a tissue-specific manner. We posit that maternally supplied ecdysone affects embryonic FoxO signaling, which ultimately plays a role in alternative morph development. Our study is one of an increasing number that implicate insulin signaling in the generation of alternative environmentally induced morphologies.

How the Barrel Cortex Became a Working Model for Developmental Plasticity: A Historical Perspective.

Abstract: For half a century now, the barrel cortex of common laboratory rodents has been an exceptionally useful model for studying the formation of topographically organized maps, neural patterning, and plasticity, both in development and in maturity We present a historical perspective on how barrels were discovered, and how thereafter, they became a workhorse for developmental neuroscientists and for studies on brain plasticity and activity-dependent modeling of brain circuits What is particularly remarkable about this sensory system is a cellular patterning that is induced by signals derived from the sensory receptors surrounding the snout whiskers and transmitted centrally to the brainstem (barrelettes), the thalamus (barreloids), and the neocortex (barrels) Injury to the sensory receptors shortly after birth leads to predictable pattern alterations at all levels of the system Mouse genetics have increased our understanding of how barrels are constructed and revealed the interplay of the molecular programs that direct axon growth and cell specification, with activity-dependent mechanisms There is an ever-rising interest in this sensory system as a neurobiological model to study development of somatotopy, patterning, and plasticity at both the morphologic and physiological levels This article is part of a group of articles commemorating the 50th anniversary of the Society for Neuroscience

Dual-Component Structural Plasticity Mediated by αCaMKII Autophosphorylation on Basal Dendrites of Cortical Layer 2/3 Neurones.

Abstract: Sensory cortex exhibits receptive field plasticity throughout life in response to changes in sensory experience and offers the experimental possibility of aligning functional changes in receptive field properties with underpinning structural changes in synapses. We looked at the effects on structural plasticity of two different patterns of whisker deprivation in male and female mice: chessboard deprivation, which causes functional plasticity; and all deprived, which does not. Using 2-photon microscopy and chronic imaging through a cranial window over the barrel cortex, we found that layer 2/3 neurones exhibit robust structural plasticity, but only in response to whisker deprivation patterns that cause functional plasticity. Chessboard pattern deprivation caused dual-component plasticity in layer 2/3 by (1) increasing production of new spines that subsequently persisted for weeks and (2) enlarging spine head sizes in the preexisting stable spine population. Structural plasticity occurred on basal dendrites, but not apical dendrites. Both components of plasticity were absent in αCaMKII-T286A mutants that lack LTP and experience-dependent potentiation in barrel cortex, implying that αCaMKII autophosphorylation is not only important for stabilization and enlargement of spines, but also for new spine production. These studies therefore reveal the relationship between spared whisker potentiation in layer 2/3 neurones and the form and mechanisms of structural plasticity processes that underlie them.SIGNIFICANCE STATEMENT This study provides a missing link in a chain of reasoning that connects LTP to experience-dependent functional plasticity in vivo We found that increases in dendritic spine formation and spine enlargement (both of which are characteristic of LTP) only occurred in barrel cortex during sensory deprivation that produced potentiation of sensory responses. Furthermore, the dendritic spine plasticity did not occur during sensory deprivation in mice lacking LTP and experience-dependent potentiation (αCaMKII autophosphorylation mutants). We also found that the dual-component dendritic spine plasticity only occurred on basal dendrites and not on apical dendrites, thereby resolving a paradox in the literature suggesting that layer 2/3 neurones lack structural plasticity in response to sensory deprivation.