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1.
Gutierrez-Mazariegos J Theodosiou M Campo-Paysaa F Schubert M 《Seminars in cell & developmental biology》2011,22(6):603-610
Extensive research carried out over the last 100 years has established that the fat-soluble organic compound vitamin A plays crucial roles in early development, organogenesis, cell proliferation, differentiation and apoptosis as well as in tissue homeostasis. Given its importance during development, the delivery of vitamin A to the embryo is very tightly regulated with perturbations leading to severe malformations. This review discusses the roles of vitamin A during human development and the molecular mechanisms controlling its biological effects, hence bridging the gap between human development and molecular genetic work carried out in animal models. Vitamin A delivery during pregnancy and its developmental teratology in humans are thus discussed alongside work on model organisms, such as chicken or mice, revealing the molecular layout and functions of vitamin A metabolism and signaling. We conclude that, during development, vitamin A-derived signals are very tightly controlled in time and space and that this complex regulation is achieved by elaborate autoregulatory loops and by sophisticated interactions with other signaling cascades. 相似文献
2.
Thermal plasticity of growth and development varies adaptively among alternative developmental pathways
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Sami M. Kivelä Beatrice Svensson Alma Tiwe Karl Gotthard 《Evolution; international journal of organic evolution》2015,69(9):2399-2413
Polyphenism, the expression of discrete alternative phenotypes, is often a consequence of a developmental switch. Physiological changes induced by a developmental switch potentially affect reaction norms, but the evolution and existence of alternative reaction norms remains poorly understood. Here, we demonstrate that, in the butterfly Pieris napi (Lepidoptera: Pieridae), thermal reaction norms of several life history traits vary adaptively among switch‐induced alternative developmental pathways of diapause and direct development. The switch was affected both by photoperiod and temperature, ambient temperature during late development having the potential to override earlier photoperiodic cues. Directly developing larvae had higher development and growth rates than diapausing ones across the studied thermal gradient. Reaction norm shapes also differed between the alternative developmental pathways, indicating pathway‐specific selection on thermal sensitivity. Relative mass increments decreased linearly with increasing temperature and were higher under direct development than diapause. Contrary to predictions, population phenology did not explain trait variation or thermal sensitivity, but our experimental design probably lacks power for finding subtle phenology effects. We demonstrate adaptive differentiation in thermal reaction norms among alternative phenotypes, and suggest that the consequences of an environmentally dependent developmental switch primarily drive the evolution of alternative thermal reaction norms in P. napi. 相似文献
3.
Breathing is a rhythmic motor behavior generated and controlled by hindbrain neuronal networks. Respiratory motor output arises from two distinct, but functionally interacting, rhythmogenic networks: the pre-B?tzinger complex (preB?tC) and the retrotrapezo?d nucleus/parafacial respiratory group (RTN/pFRG). This review outlines recent advances in delineating the genetic specification of the neuronal constituents of these two rhythmogenic networks, their respective roles in respiratory function and how they interact to constitute a functional respiratory circuit ensemble. The often lethal consequences of disruption to these networks found in naturally occurring developmental disorders, transgenic animals, and highly specific lesion studies are described. In addition, we discuss how recent computational models enhance our understanding of how respiratory networks generate and regulate respiratory behavior. 相似文献
4.
Macroautophagy is a process of regulated turnover of cellular constituents that occurs during development and under conditions of stress such as starvation. Defects in autophagy have serious consequences, as they have been linked to neurodegenerative disease, cancer, and cardiomyopathy. This process, which exists in all eukaryotic cells, is tightly controlled, but in extreme cases results in the death of the cell. While major insights into the molecular and biochemical pathways involved have come from genetic studies in yeast, little is known about autophagic pathways in mammalian cells, particularly in neurons. Recently, research in neuronal culture models has begun to identify some characteristics of neuronal macroautophagy. The results suggest that macroautophagy in neurons may provide a neuroprotective mechanism. Here, we review the defining characteristics of autophagy with special attention to its role in neurodegenerative disorders, and recent efforts to delineate the pathway of autophagic protein degradation in neurons. 相似文献
5.
In multicellular organisms, cells cooperate within a well-defined developmental program. Cancer is a breakdown of such cooperation: cells mutate to phenotypes of uncoordinated proliferation. We study basic principles of the architecture of solid tissues that influence the rate of cancer initiation. In particular, we explore how somatic selection acts to prevent or to promote cancer. Cells with mutations in oncogenes or tumor suppressor genes often have increased proliferation rates. Somatic selection increases their abundance and thus enhances the risk of cancer. Many potentially harmful mutations, however, increase the probability of triggering apoptosis and, hence, initially lead to cells with reduced net proliferation rates. Such cells are eliminated by somatic selection, which therefore also works to reduce the risk of cancer. We show that a tissue organization into small compartments avoids the rapid spread of mutations in oncogenes and tumor suppressor genes, but promotes genetic instability. In small compartments, genetic instability, which confers a selective disadvantage for the cell, can spread by random drift. If both deleterious and advantageous mutations participate in tumor initiation, then we find an intermediate optimum for the compartment size. 相似文献
6.
《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2020,1867(3):118461
Cardiac diseases, characterized by cardiomyocyte loss, lead to dramatic impairment of cardiac function and ultimately to congestive heart failure. Despite significant advances, conventional treatments do not correct the defects in cardiac muscle cell numbers and the prognosis of congestive heart failure remains poor. The existence, in adult mammalian heart, of low but detectable cardiomyocyte proliferative capacities has shifted the target of regenerative therapy toward new therapeutical strategy. Indeed, the stimulation of terminally differentiated cardiomyocyte proliferation represents the main therapeutic approach for heart regeneration. Increasing evidence demonstrating that the loss of mammalian cardiomyocyte renewal potential shortly after birth causes the loss of regenerative capacities, strongly support the hypothesis that a detailed understanding of the molecular mechanisms controlling fetal and postnatal cardiomyocyte proliferation is essential to identify targets for cardiac regeneration. Here, we will review major developmental mechanisms regulating fetal cardiomyocyte proliferation and will describe the impact of the developmental switch, operating at birth and driving postnatal heart maturation, on the regulation of adult cardiomyocyte proliferation, all these mechanisms representing potential targets for cardiac repair and regeneration. 相似文献
7.
Sprouty proteins: multifaceted negative-feedback regulators of receptor tyrosine kinase signaling 总被引:15,自引:0,他引:15
Receptor tyrosine kinases (RTKs) control a wide variety of processes in multicellular organisms, including proliferation, differentiation, migration and survival. Their activity is tightly controlled through the coordinated action of both positive and negative regulators that function at multiple levels of the signal transduction cascade, and at different time points within the growth-factor-induced response. When this process goes awry, the outcome can be developmental defects and malignancy. Sprouty (Spry) proteins represent a major class of ligand-inducible inhibitors of RTK-dependent signaling pathways. New biochemical and genetic evidence indicates specific roles of the Spry genes in development and multiple modes of action of the Spry proteins in regulation of the RTK-induced response. 相似文献
8.
9.
细胞发育是细胞内各种复杂反应在时间和空间上有序协调的过程, 包括细胞增殖、胞质分裂、细胞运动、细胞分化和组织生成等.作为G蛋白家族重要成员的RhoA起了重要的调控作用:在G蛋白调控因子(如GEF XPLN、 p115RhoGEF、p190RhoGAP等)的作用下,活化的RhoA依次与效应蛋白分子(如ROCK1/2、 mDia、 PRK1/2、 citron 激酶等)结合, 从而开启了下游的信号通路, 最终使细胞能够迅速地对外界刺激做出反应.干细胞是一类既能自我更新又能特异分化形成终末分化细胞的细胞, 而 RhoA对干细胞的自我更新和定向分化也起着“开关"作用, 对RhoA信号通路的调节调控了胚胎发生、神经发生、造血生成及成骨和肌肉生成等干细胞分化发育过程.肿瘤是正常细胞在各种因素长期作用下增殖异常的产物, 而RhoA异常表达与肿瘤的发生、侵润与转移密切相关, RhoA信号通路与p53等基因的交互作用在肿瘤的发育过程中也发挥了重要的作用. 相似文献
10.
Xinying Zhu Jinxia Qiu Tao Zhang Yaping Yang Shuai Guo Tianshun Li Kangfeng Jiang Arshad Zahoor Ganzhen Deng Changwei Qiu 《Journal of cellular physiology》2020,235(3):2389-2402
Breast cancer is a common malignancy that is highly lethal with poor survival rates and immature therapeutics that urgently needs more effective and efficient therapies. MicroRNAs are intrinsically involved in different cancer remedies, but their mechanism in breast cancer has not been elucidated for prospective treatment. The function and mechanism of microRNA-188-5p (miR-188) have not been thoroughly investigated in breast cancer. In our study, we found that the expression of miR-188 in breast cancer tissues was obviously reduced. Our findings also revealed the abnormal overexpression of miR-188 in 4T1 and MCF-7 cells significantly suppressed cell proliferation and migration and also enhanced apoptosis. miR-188 induced cell cycle arrest in the G1 phase. To illuminate the molecular mechanism of miR-188, Rap2c was screened as a single target gene by bioinformatics database analysis and was further confirmed by dual-luciferase assay. Moreover, Rap2c was found to be a vital molecular switch for the mitogen-activated protein kinase signaling pathway in tumor progression by decreasing apoptosis and promoting proliferation and migration. In conclusion, our results revealed that miR-188 is a cancer progression suppressor and a promising future target for breast cancer therapy. 相似文献
11.
Sundström LF Lõhmus M Devlin RH 《Evolution; international journal of organic evolution》2005,59(7):1560-1569
Substantial evidence from the animal kingdom shows that there is a trade-off between benefits and costs associated with rapid somatic growth. One would therefore expect growth rates under natural conditions to be close to an evolutionary optimum. Nevertheless, natural selection in many salmonid species appears to be toward larger size and earlier emergence from spawning redds, indicating a potential for increased growth rate to evolve. We tested how selection for genetic variants (growth hormone transgenic coho salmon, Oncorhynchus kisutch, with more than doubled daily growth rate potential relative to wild genotypes) depended on predator timing and food abundance during the early period of life (fry stage). In artificial redds, fry of the fast-growing genotypes showed a highly significant developmental shift, emerging from gravel nests approximately two weeks sooner, but with an 18.6% reduced survival, relative to wild-genotype fry. In seminatural streams, fry of the fast-growing genotypes suffered higher predation than those of wild genotypes when predators were present at the time of fry emergence, but this difference was less pronounced when food was scarce. In streams where predators were introduced after emergence, fry survived equally well regardless of food availability. Surviving fry grew faster in habitats provided with more food, and fast-growing genotypes also grew faster than wild genotypes when predators arrived late and food was abundant. Fewer fish migrated downstream past a waterfall when food availability was high and in the presence of predators, and wild-genotype fry were more likely to migrate than fry of the fast-growing genotypes. After being returned to the experimental streams after migration, fast-growing genotypes survived equally well as those of the same genotypes that did not migrate, whereas migrating wild genotypes experienced higher mortality relative to those of the same genotypes that did not migrate. Comparisons of growth rates between siblings retained under hatchery conditions and those from habitats with the fastest growth in the experimental stream revealed that growth rates were similar for wild genotypes in both environments, whereas the fast-growing genotypes in the streams only realized 90% of their growth potential. The present study has shown that a major shift in developmental timing can alter critical early stages affecting survival and can have a significant effect on fitness. Furthermore, ecological conditions such as food abundance and predation pressure can strongly influence the potential for fast-growing variants to survive under natural conditions. The large-scale removal of many predatory species around the world may augment the evolution of increased intrinsic growth rates in some taxa. 相似文献
12.
Population genetics of the Y chromosome of Drosophila melanogaster: rDNA variation and phenotypic correlates 总被引:1,自引:0,他引:1
One means of examining the evolutionary significance of molecular variation on the Y chromosome is to identify phenotypes specifically affected by Y-linked genes, and to quantify the phenotypic variation and its correlation to the molecular variation. The functional importance of the Y-linked array of rRNA genes is demonstrated by the ability of Y chromosome to rescue X-linked bobbed lethal alleles, whose lethality is seen in homozygous females. Because low numbers of X-linked rDNA gene copies result in increased developmental time and shortened bristles, and because there is considerable natural variation in Y-linked copy number, a careful examination of Y-linked variation in these two traits may uncover a mode of selection acting on the multigene family. In this study, 36 Y-chromosome replacement lines were tested to detect subtle variation in bristle phenotypes and developmental rates. Correlations among these traits, rDNA gene copy number, and intergenic sequence length were quantified. The absence of significant correlations between phenotypic characters and rDNA copy number of intergenic sequence length suggests that the extant molecular variation in Y-linked rDNA can have at most very small selective effects. 相似文献
13.
《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2020,1865(9):158737
Aberrant fatty acid (FA) metabolism is a hallmark of proliferating cells, including untransformed fibroblasts or cancer cells. Lipolysis of intracellular triglyceride (TG) stores by adipose triglyceride lipase (ATGL) provides an important source of FAs serving as energy substrates, signaling molecules, and precursors for membrane lipids. To investigate if ATGL-mediated lipolysis impacts cell proliferation, we modified ATGL activity in murine embryonic fibroblasts (MEFs) and in five different cancer cell lines to determine the consequences on cell growth and metabolism. Genetic or pharmacological inhibition of ATGL in MEFs causes impaired FA oxidation, decreased ROS production, and a substrate switch from FA to glucose leading to decreased AMPK-mTOR signaling and higher cell proliferation rates. ATGL expression in these cancer cells is low when compared to MEFs. Additional ATGL knockdown in cancer cells did not significantly affect cellular lipid metabolism or cell proliferation whereas the ectopic overexpression of ATGL increased lipolysis and reduced proliferation. In contrast to ATGL silencing, pharmacological inhibition of ATGL by Atglistatin© impeded the proliferation of diverse cancer cell lines, which points at an ATGL-independent effect. Our data indicate a crucial role of ATGL-mediated lipolysis in the regulation of cell proliferation. The observed low ATGL activity in cancer cells may represent an evolutionary selection process and mechanism to sustain high cell proliferation rates. As the increasing ATGL activity decelerates proliferation of five different cancer cell lines this may represent a novel therapeutic strategy to counteract uncontrolled cell growth. 相似文献
14.
Hastings IM 《Genetical research》2000,75(1):107-114
Standard theory provides a simple prediction for the frequency of a recessive lethal allele conferring heterozygous protection against an infectious disease (the best-known example being sickle cell protection against malaria). This relationship allows historic disease mortality rates to be estimated. There are, however, hidden biases in this approach. Reproductively active human females in archaic societies normally produce children at intervals of around 4 years. If death of the fetus or young infant (less than around 3 years of age) occurs, then the mother re-enters oestrus and produces another child. This 'reproductive compensation' reduces selection against the agent causing early mortality (the recessive allele or infective agent) and biases our estimates of historic mortality rates. The magnitude of these biases is investigated. Re-conception also constitutes a demographic selective pressure acting alongside natural selection: lethal genetic diseases (or tightly linked loci) will be selected to become ever more virulent, killing at ever decreasing ages, to allow the mother to re-enter oestrus and re-conceive a (hopefully unaffected) sibling; this effect also invalidates statistical tests using the number of alleles to distinguish overdominance from drift as explanations for high allele frequency. The same bias affects calculations of mutation/selection balance: for any given mutation rate, syndromes which kill early in life will reach much higher frequencies than those killing at later ages. An intriguing consequence is that lethal recessive disorders in humans will increase in frequency by up to 45% as a consequence of the recent demographic transition to planned family size. 相似文献
15.
Baehrecke EH 《Nature reviews. Molecular cell biology》2002,3(10):779-787
The formation of an adult animal from a fertilized embryo involves the production and death of cells. Surprisingly, many cells are produced during development with an ultimate fate of death, and defects in programmed cell death can result in developmental abnormalities. Recent studies indicate that cells can die by many different mechanisms, and these differences have implications for proper animal development and disorders such as cancer and autoimmunity. 相似文献
16.
The unique size and complexity of the human cerebral cortex are achieved via a long and precisely regulated developmental process controlling neurogenesis, neuronal migration and differentiation. Traditionally, disorders of cortical development have been classified on the basis of the most obvious defects in one of these developmental steps. However, the more we learn about the cellular biological roles of genes that are essential for cortical development, the more we realize that these functions map onto molecular processes, but not so cleanly onto anatomical processes. Essential genes might be involved in both proliferation and migration as well as differentiation, reflecting roles for underlying molecular mechanisms in different phases of development and causing a stunning variety of cortical defects. 相似文献
17.
Selective processes in development: implications for the costs and benefits of phenotypic plasticity
Snell-Rood EC 《Integrative and comparative biology》2012,52(1):31-42
Adaptive phenotypic plasticity, the ability of a genotype to develop a phenotype appropriate to the local environment, allows organisms to cope with environmental variation and has implications for predicting how organisms will respond to rapid, human-induced environmental change. This review focuses on the importance of developmental selection, broadly defined as a developmental process that involves the sampling of a range of phenotypes and feedback from the environment reinforcing high-performing phenotypes. I hypothesize that understanding the degree to which developmental selection underlies plasticity is key to predicting the costs, benefits, and consequences of plasticity. First, I review examples that illustrate that elements of developmental selection are common across the development of many different traits, from physiology and immunity to circulation and behavior. Second, I argue that developmental selection, relative to a fixed strategy or determinate (switch) mechanisms of plasticity, increases the probability that an individual will develop a phenotype best matched to the local environment. However, the exploration and environmental feedback associated with developmental selection is costly in terms of time, energy, and predation risk, resulting in major changes in life history such as increased duration of development and greater investment in individual offspring. Third, I discuss implications of developmental selection as a mechanism of plasticity, from predicting adaptive responses to novel environments to understanding conditions under which genetic assimilation may fuel diversification. Finally, I outline exciting areas of future research, in particular exploring costs of selective processes in the development of traits outside of behavior and modeling developmental selection and evolution in novel environments. 相似文献
18.
The development of the central nervous system can be divided into a number of phases, each of which can be subject of genetic or epigenetic alterations that may originate particular developmental disorders. In recent years, much progress has been made in elucidating the molecular and cellular mechanisms by which the vertebrate forebrain develops. Therefore, our understanding of major developmental brain disorders such as cortical malformations and neuronal migration disorders has significantly increased. In this review, we will describe the major stages in forebrain morphogenesis and regionalization, with special emphasis on developmental molecular mechanisms derailing telencephalic development with subsequent damage to cortical function. Because animal models, mainly mouse, have been fundamental for this progress, we will also describe some characteristic mouse models that have been capital to explore these molecular mechanisms of malformative diseases of the human brain. Although most of the genes involved in the regulation of basic developmental processes are conserved among vertebrates, the extrapolation of mouse data to corresponding gene expression and function in humans needs careful individual analysis in each functional system. 相似文献
19.
The development of the central nervous system can be divided into a number of phases, each of which can be subject of genetic or epigenetic alterations that may originate particular developmental disorders. In recent years, much progress has been made in elucidating the molecular and cellular mechanisms by which the vertebrate forebrain develops. Therefore, our understanding of major developmental brain disorders such as cortical malformations and neuronal migration disorders has significantly increased. In this review, we will describe the major stages in forebrain morphogenesis and regionalization, with special emphasis on developmental molecular mechanisms derailing telencephalic development with subsequent damage to cortical function. Because animal models, mainly mouse, have been fundamental for this progress, we will also describe some characteristic mouse models that have been capital to explore these molecular mechanisms of malformative diseases of the human brain. Although most of the genes involved in the regulation of basic developmental processes are conserved among vertebrates, the extrapolation of mouse data to corresponding gene expression and function in humans needs careful individual analysis in each functional system. 相似文献