Apoptosis and development

2003 ◽  
Vol 39 ◽  
pp. 11-24 ◽  
Author(s):  
Justin V McCarthy
Keyword(s):  
Drosophila Melanogaster ◽  
Mammalian Cells ◽  
Cell Number ◽  
Model Organisms ◽  
Biological Processes ◽  
Nematode Caenorhabditis Elegans ◽  
Apoptotic Pathway ◽  
Genetic Pathways ◽  
Evolutionarily Conserved ◽  
Multicellular Organisms

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

scholarly journals Optimization of Dietary Restriction Protocols in Drosophila

2007 ◽  
Vol 62 (10) ◽  
pp. 1071-1081 ◽  
Author(s):  
Timothy M. Bass ◽  
Richard C. Grandison ◽  
Richard Wong ◽  
Pedro Martinez ◽  
Linda Partridge ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Adverse Effects ◽  
Life Span ◽  
Dietary Restriction ◽  
Food Composition ◽  
Model Organisms ◽  
Nutritional Content ◽  
Evolutionarily Conserved ◽  
Interspecific Comparisons

Abstract Dietary restriction (DR) extends life span in many organisms, through unknown mechanisms that may or may not be evolutionarily conserved. Because different laboratories use different diets and techniques for implementing DR, the outcomes may not be strictly comparable. This complicates intra- and interspecific comparisons of the mechanisms of DR and is therefore central to the use of model organisms to research this topic. Drosophila melanogaster is an important model for the study of DR, but the nutritional content of its diet is typically poorly defined. We have compared fly diets composed of different yeasts for their effect on life span and fecundity. We found that only one diet was appropriate for DR experiments, indicating that much of the published work on fly “DR” may have included adverse effects of food composition. We propose procedures to ensure that diets are suitable for the study of DR in Drosophila.

Super models

2003 ◽  
Vol 13 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Maureen M. Barr
Keyword(s):  
Model Organism ◽  
Model System ◽  
Biological Pathways ◽  
Cellular Biology ◽  
Model Organisms ◽  
Biological Processes ◽  
Nematode Caenorhabditis Elegans ◽  
Yeast Saccharomyces Cerevisiae ◽  
Experimental Systems ◽  
Genomics And Proteomics

Model organisms have been used over a century to understand basic, conserved biological processes. The study of these experimental systems began with genetics and development, moved into molecular and cellular biology, and most recently propelled into functional genomics and proteomics. The goal of this review is simple: to discuss the place of model organisms in “The Age of the Ome”: the genome, the transcriptome, and the proteome. This review will address the following questions. What exactly is a model organism? What characteristics make an excellent model system? Using the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans as examples, this review will discuss these issues with the aim of demonstrating how model organisms remain indispensable scientific tools for understanding complex biological pathways and human disease.

scholarly journals Human Bak induces cell death in Schizosaccharomyces pombe with morphological changes similar to those with apoptosis in mammalian cells.

1997 ◽  
Vol 17 (5) ◽  
pp. 2468-2474 ◽  
Author(s):  
B Ink ◽  
M Zörnig ◽  
B Baum ◽  
N Hajibagheri ◽  
C James ◽  
...  
Keyword(s):  
Cell Death ◽  
Schizosaccharomyces Pombe ◽  
Mammalian Cells ◽  
Morphological Changes ◽  
Yeast Cells ◽  
Bh3 Domain ◽  
Evolutionarily Conserved ◽  
Unicellular Organisms ◽  
Induction Of Apoptosis ◽  
Multicellular Organisms

Apoptosis as a form of programmed cell death (PCD) in multicellular organisms is a well-established genetically controlled process that leads to elimination of unnecessary or damaged cells. Recently, PCD has also been described for unicellular organisms as a process for the socially advantageous regulation of cell survival. The human Bcl-2 family member Bak induces apoptosis in mammalian cells which is counteracted by the Bcl-x(L) protein. We show that Bak also kills the unicellular fission yeast Schizosaccharomyces pombe and that this is inhibited by coexpression of human Bcl-x(L). Moreover, the same critical BH3 domain of Bak that is required for induction of apoptosis in mammalian cells is also required for inducing death in yeast. This suggests that Bak kills mammalian and yeast cells by similar mechanisms. The phenotype of the Bak-induced death in yeast involves condensation and fragmentation of the chromatin as well as dissolution of the nuclear envelope, all of which are features of mammalian apoptosis. These data suggest that the evolutionarily conserved metazoan PCD pathway is also present in unicellular yeast.

scholarly journals Cell fitness is an omniphenotype

2018 ◽  
Author(s):  
Nicholas C. Jacobs ◽  
Ji Woong Park ◽  
Timothy R. Peterson
Keyword(s):  
Mammalian Cells ◽  
Disease Model ◽  
Environmental Variable ◽  
Cell Number ◽  
Model Organisms ◽  
Number Of Factors ◽  
Human Genes ◽  
New Gene ◽  
Altered Cell ◽  
The Cost

ABSTRACTGenotype-phenotype relationships are at the heart of biology and medicine. Numerous advances in genotyping and phenotyping have accelerated the pace of disease gene and drug discovery. Though now that there are so many genes and drugs to study, it makes prioritizing them difficult. Also, disease model assays are getting more complex and this is reflected in the growing complexity of research papers and the cost of drug development. Herein we propose a way out of this arms race. We argue for synthetic interaction testing in mammalian cells using cell fitness – which reflect changes in cell number that could be due to a number of factors – as a readout to judge the potential of a genetic or environmental variable of interest (e.g., a gene or drug). That is, if an unknown perturbation of a mammalian gene or drug of interest is combined with a known perturbation and causes a strong cell fitness phenotype relative to that caused by the known perturbation alone, this justifies proceeding with the new gene/drug in more complex models like mouse models where the known perturbation is already validated. This recommendation is backed by the following: 1) human genes essential for cell growth involve nearly all classifications of cellular and molecular processes; 2) Nearly all human genes important in cancer – a disease defined by altered cell number – are also important in other complex diseases; 3) Many drugs affect a patient’s condition and the fitness of their cells comparably. Taken together, these findings suggest cell fitness could be a broadly applicable phenotype for understanding gene and drug function. Measuring cell fitness is robust and requires little time and money. These are features that have long been capitalized on by pioneers using model organisms that we hope more mammalian biologists will recognize.

scholarly journals Identification and In Vivo Characterisation of Cardioactive Peptides in Drosophila melanogaster

2018 ◽  
Vol 20 (1) ◽  
pp. 2 ◽  
Author(s):  
Ronja Schiemann ◽  
Kay Lammers ◽  
Maren Janz ◽  
Jana Lohmann ◽  
Achim Paululat ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Heart Function ◽  
Transgenic Animals ◽  
Peptide Hormones ◽  
Biological Processes ◽  
Functional Conservation ◽  
Regulatory Systems ◽  
Evolutionarily Conserved ◽  
Diastolic Interval

Neuropeptides and peptide hormones serve as critical regulators of numerous biological processes, including development, growth, reproduction, physiology, and behaviour. In mammals, peptidergic regulatory systems are complex and often involve multiple peptides that act at different levels and relay to different receptors. To improve the mechanistic understanding of such complex systems, invertebrate models in which evolutionarily conserved peptides and receptors regulate similar biological processes but in a less complex manner have emerged as highly valuable. Drosophila melanogaster represents a favoured model for the characterisation of novel peptidergic signalling events and for evaluating the relevance of those events in vivo. In the present study, we analysed a set of neuropeptides and peptide hormones for their ability to modulate cardiac function in semi-intact larval Drosophila melanogaster. We identified numerous peptides that significantly affected heart parameters such as heart rate, systolic and diastolic interval, rhythmicity, and contractility. Thus, peptidergic regulation of the Drosophila heart is not restricted to chronotropic adaptation but also includes inotropic modulation. By specifically interfering with the expression of corresponding peptides in transgenic animals, we assessed the in vivo relevance of the respective peptidergic regulation. Based on the functional conservation of certain peptides throughout the animal kingdom, the identified cardiomodulatory activities may be relevant not only to proper heart function in Drosophila, but also to corresponding processes in vertebrates, including humans.

Physiological and molecular mechanisms of salt and water homeostasis in the nematode Caenorhabditis elegans

2013 ◽  
Vol 305 (3) ◽  
pp. R175-R186 ◽  
Author(s):  
Keith P. Choe
Keyword(s):  
Caenorhabditis Elegans ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Model Organisms ◽  
Nematode Caenorhabditis Elegans ◽  
Water Homeostasis ◽  
Hypertonic Stress ◽  
Genetic Mechanisms ◽  
Multicellular Organisms

Intracellular salt and water homeostasis is essential for all cellular life. Extracellular salt and water homeostasis is also important for multicellular organisms. Many fundamental mechanisms of compensation for osmotic perturbations are well defined and conserved. Alternatively, molecular mechanisms of detecting salt and water imbalances and regulating compensatory responses are generally poorly defined for animals. Throughout the last century, researchers studying vertebrates and vertebrate cells made critical contributions to our understanding of osmoregulation, especially mechanisms of salt and water transport and organic osmolyte accumulation. Researchers have more recently started using invertebrate model organisms with defined genomes and well-established methods of genetic manipulation to begin defining the genes and integrated regulatory networks that respond to osmotic stress. The nematode Caenorhabditis elegans is well suited to these studies. Here, I introduce osmoregulatory mechanisms in this model, discuss experimental advantages and limitations, and review important findings. Key discoveries include defining genetic mechanisms of osmolarity sensing in neurons, identifying protein damage as a sensor and principle determinant of hypertonic stress resistance, and identification of a putative sensor for hypertonic stress associated with the extracellular matrix. Many of these processes and pathways are conserved and, therefore, provide new insights into salt and water homeostasis in other animals, including mammals.

scholarly journals The Evolutionary Conserved Transmembrane BAX Inhibitor Motif (TMBIM) Containing Protein Family Members 5 and 6 Are Essential for the Development and Survival of Drosophila melanogaster

2021 ◽  
Vol 9 ◽  
Author(s):  
Li Zhang ◽  
Sebastian Buhr ◽  
Aaron Voigt ◽  
Axel Methner
Keyword(s):  
Drosophila Melanogaster ◽  
Mammalian Cells ◽  
Developmental Stages ◽  
Family Members ◽  
Protein Family ◽  
Expression Levels ◽  
Atp Production ◽  
Evolutionarily Conserved ◽  
Human Proteins ◽  
Er Calcium

The mammalian Transmembrane BAX Inhibitor Motif (TMBIM) protein family consists of six evolutionarily conserved hydrophobic proteins that affect programmed cell death and the regulation of intracellular calcium levels. The bacterial ortholog BsYetJ is a pH-dependent calcium channel. We here identified seven TMBIM family members in Drosophila melanogaster and describe their expression levels in diverse tissues and developmental stages. A phylogenetic analysis revealed that CG30379 represents the ortholog of human TMBIM4 although these two proteins are much less related than TMBIM5 (CG2076 and CG1287/Mics1) and TMBIM6 (CG7188/Bi-1) to their respective orthologs. For TMBIM1-3 the assignment is more dubious because the fly and the human proteins cluster together. We conducted a functional analysis based on expression levels and the availability of RNAi lines. This revealed that the ubiquitous knockdown of CG3798/Nmda1 and CG3814/Lfg had no effect on development while knockdown of CG2076/dTmbim5 resulted in death at the pupa stage and knockdown of CG7188/dTmbim6 in death at the embryonic stage. Ubiquitous knockdown of the second TMBIM5 paralog CG1287/Mics1 ensued in male sterility. Knockdown of dTmbim5 and 6 in muscle and neural tissue also greatly reduced lifespan through different mechanisms. Knockdown of the mitochondrial family member dTmbim5 resulted in reduced ATP production and a pro-apoptotic expression profile while knockdown of the ER protein dTmbim6 increased the ER calcium levels similar to findings in mammalian cells. Our data demonstrate that dTmbim5 and 6 are essential for fly development and survival but affect cell survival through different mechanisms.

scholarly journals The secret lives of Drosophila flies

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Therese Ann Markow
Keyword(s):  
Drosophila Melanogaster ◽  
Natural History ◽  
Empirical Studies ◽  
Model Organisms ◽  
Biological Processes ◽  
Wild Populations

Flies of the genus Drosophila, and particularly those of the species Drosophila melanogaster, are best known as laboratory organisms. As with all model organisms, they were domesticated for empirical studies, but they also continue to exist as wild populations.Decades of research on these flies in the laboratory have produced astounding and important insights into basic biological processes, but we have only scratched the surface of what they have to offer as research organisms. An outstanding challenge now is to build on this knowledge and explore how natural history has shaped D. melanogaster in order to advance our understanding of biology more generally.

scholarly journals Patterns of microsatellite distribution reflect the evolution of biological complexity

2018 ◽  
Author(s):  
Surabhi Srivastava ◽  
Akshay Kumar Avvaru ◽  
Divya Tej Sowpati ◽  
Rakesh K Mishra
Keyword(s):  
Related Species ◽  
Cell Types ◽  
Model Organisms ◽  
Closely Related Species ◽  
Repeat Elements ◽  
Evolutionary Selection ◽  
Coding Regions ◽  
Evolutionarily Conserved ◽  
Species Specific ◽  
Multicellular Organisms

AbstractMicrosatellites, also known as Simple Sequence Repeats (SSRs), are evolutionarily conserved repeat elements distributed non-randomly in all genomes. Many studies have investigated their pattern of occurrence in order to understand their role, but their identification has largely been non-exhaustive and limited to a few related species or model organisms. Here, we identify ~685 million microsatellites from 719 eukaryotes and analyze their evolutionary trends from protists to mammals. We document novel patterns uniquely demarcating closely related species, including in pathogens like Leishmania as well as in higher organisms such as Drosophila, birds, primates, and cereal crops. The distribution of SSRs in coding and non-coding regions reveals taxon-specific variations in their exonic, intronic and intergenic densities. We also show that specific SSRs accumulate at longer lengths in higher organisms indicating an evolutionary selection pressure. In general, we observe greater constraints in the SSR composition of multicellular organisms with complex cell types, while simpler organisms show more diversity. The conserved microsatellite trends and species-specific signatures identified in this study closely mirror phylogenetic relationships and we hypothesize that SSRs are integral components in speciation and the evolution of organismal complexity. The microsatellite dataset generated in this work provides a large number of candidates for functional analysis and unparalleled scope for understanding their roles across the evolutionary landscape.

scholarly journals JNK-mediated Slit-Robo signaling facilitates epithelial wound repair by extruding dying cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chiaki Iida ◽  
Shizue Ohsawa ◽  
Kiichiro Taniguchi ◽  
Masatoshi Yamamoto ◽  
Ginés Morata ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Wound Repair ◽  
Physical Injury ◽  
Biological Processes ◽  
Jnk Signaling ◽  
Evolutionarily Conserved ◽  
Growth Factor Genes ◽  
Multicellular Organisms ◽  
Dying Cells

AbstractMulticellular organisms repair injured epithelium by evolutionarily conserved biological processes including activation of c-Jun N-terminal kinase (JNK) signaling. Here, we show in Drosophila imaginal epithelium that physical injury leads to the emergence of dying cells, which are extruded from the wounded tissue by JNK-induced Slit-Roundabout2 (Robo2) repulsive signaling. Reducing Slit-Robo2 signaling in the wounded tissue suppresses extrusion of dying cells and generates aberrant cells with highly upregulated growth factors Wingless (Wg) and Decapentaplegic (Dpp). The inappropriately elevated Wg and Dpp impairs wound repair, as halving one of these growth factor genes cancelled wound healing defects caused by Slit-Robo2 downregulation. Our data suggest that JNK-mediated Slit-Robo2 signaling contributes to epithelial wound repair by promoting extrusion of dying cells from the wounded tissue, which facilitates transient and appropriate induction of growth factors for proper wound healing.

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