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Tissue Engineering. Part A Sep 2008The reorganization of epithelial sheets into tubes is a fundamental process in the formation of many organs, such as the lungs, kidneys, gut, and neural tube. This... (Review)
Review
The reorganization of epithelial sheets into tubes is a fundamental process in the formation of many organs, such as the lungs, kidneys, gut, and neural tube. This process involves the patterning of distinct cell types and the coordination of those cells during the shape changes and rearrangements that produce the tube. A better understanding of the cellular and genetic mechanisms that regulate tube formation is necessary for tissue engineers to develop functional organs in vitro. The Drosophila egg chamber has emerged as an outstanding model for studying tubulogenesis. Synthesis of the dorsal respiratory appendages by the follicular epithelium resembles primary neurulation in vertebrates. This review summarizes work on the patterning and morphogenesis of the dorsal-appendage tubes and highlights key areas where mathematical modeling could contribute to our understanding of these processes.
Topics: Animals; Cell Movement; Drosophila; Drosophila Proteins; Female; Gene Expression Regulation, Developmental; Oogenesis; Ovum
PubMed: 18707228
DOI: 10.1089/ten.tea.2008.0124 -
Genome Biology 2007A recent report describes the identification through the use of in vitro selection of a peptide that antagonizes Methuselah signaling in Drosophila in vitro and extends... (Review)
Review
A recent report describes the identification through the use of in vitro selection of a peptide that antagonizes Methuselah signaling in Drosophila in vitro and extends fly life span in vivo.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Drug Design; Ligands; Longevity; Oligopeptides; Protein Conformation; Receptors, G-Protein-Coupled
PubMed: 17764591
DOI: 10.1186/gb-2007-8-8-222 -
Neural Development Oct 2022The paths axons travel to reach their targets and the subsequent synaptic connections they form are highly stereotyped. How cell surface proteins (CSPs) mediate these...
The paths axons travel to reach their targets and the subsequent synaptic connections they form are highly stereotyped. How cell surface proteins (CSPs) mediate these processes is not completely understood. The Drosophila neuromuscular junction (NMJ) is an ideal system to study how pathfinding and target specificity are accomplished, as the axon trajectories and innervation patterns are known and easily visualized. Dpr10 is a CSP required for synaptic partner choice in the neuromuscular and visual circuits and for axon pathfinding in olfactory neuron organization. In this study, we show that Dpr10 is also required for motor axon pathfinding. To uncover how Dpr10 mediates this process, we used immunoprecipitation followed by mass spectrometry to identify Dpr10 associated proteins. One of these, Nocte, is an unstructured, intracellular protein implicated in circadian rhythm entrainment. We mapped nocte expression in larvae and found it widely expressed in neurons, muscles, and glia. Cell-specific knockdown suggests nocte is required presynaptically to mediate motor axon pathfinding. Additionally, we found that nocte and dpr10 genetically interact to control NMJ assembly, suggesting that they function in the same molecular pathway. Overall, these data reveal novel roles for Dpr10 and its newly identified interactor, Nocte, in motor axon pathfinding and provide insight into how CSPs regulate circuit assembly.
Topics: Animals; Drosophila; Axon Guidance; Motor Neurons; Axons; Drosophila Proteins; Membrane Proteins
PubMed: 36271407
DOI: 10.1186/s13064-022-00165-5 -
Epigenetics Nov 2020Ten-eleven Translocation (TET) proteins have emerged as a family of epigenetic regulators that are important during development and have been implicated in various types... (Review)
Review
Ten-eleven Translocation (TET) proteins have emerged as a family of epigenetic regulators that are important during development and have been implicated in various types of cancers. TET is a highly conserved protein that has orthologues in almost all multicellular organisms. Here, we review recent literature on the novel substrate specificity of this family of DNA 5-methylcytosine demethylases on DNA 6-methyladenine and RNA 5-methylcytosine that were first identified in the invertebrate model . We focus on the biological role of these novel epigenetic marks in the fruit fly and mammals and highlight TET proteins' critical function during development specifically in brain development.
Topics: Animals; DNA Methylation; Drosophila; Drosophila Proteins; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Mixed Function Oxygenases
PubMed: 32419604
DOI: 10.1080/15592294.2020.1767323 -
Current Biology : CB Aug 2003
Topics: Animals; Drosophila Proteins; Membrane Proteins; Serine Endopeptidases
PubMed: 12906806
DOI: 10.1016/s0960-9822(03)00519-0 -
Cells Feb 2024Cell death plays an essential function in organismal development, wellbeing, and ageing. Many types of cell deaths have been described in the past 30 years. Among these,... (Review)
Review
Cell death plays an essential function in organismal development, wellbeing, and ageing. Many types of cell deaths have been described in the past 30 years. Among these, apoptosis remains the most conserved type of cell death in metazoans and the most common mechanism for deleting unwanted cells. Other types of cell deaths that often play roles in specific contexts or upon pathological insults can be classed under variant forms of cell death and programmed necrosis. Studies in have contributed significantly to the understanding and regulation of apoptosis pathways. In addition to this, has also served as an essential model to study the genetic basis of autophagy-dependent cell death (ADCD) and other relatively rare types of context-dependent cell deaths. Here, we summarise what is known about apoptosis, ADCD, and other context-specific variant cell death pathways in , with a focus on developmental cell death.
Topics: Animals; Drosophila; Cell Death; Apoptosis; Drosophila Proteins; Autophagic Cell Death
PubMed: 38391960
DOI: 10.3390/cells13040347 -
PloS One 2017Chorea-Acanthocytosis is a rare, neurodegenerative disorder characterized by progressive loss of locomotor and cognitive function. It is caused by loss of function...
Chorea-Acanthocytosis is a rare, neurodegenerative disorder characterized by progressive loss of locomotor and cognitive function. It is caused by loss of function mutations in the Vacuolar Protein Sorting 13A (VPS13A) gene, which is conserved from yeast to human. The consequences of VPS13A dysfunction in the nervous system are still largely unspecified. In order to study the consequences of VPS13A protein dysfunction in the ageing central nervous system we characterized a Drosophila melanogaster Vps13 mutant line. The Drosophila Vps13 gene encoded a protein of similar size as human VPS13A. Our data suggest that Vps13 is a peripheral membrane protein located to endosomal membranes and enriched in the fly head. Vps13 mutant flies showed a shortened life span and age associated neurodegeneration. Vps13 mutant flies were sensitive to proteotoxic stress and accumulated ubiquitylated proteins. Levels of Ref(2)P, the Drosophila orthologue of p62, were increased and protein aggregates accumulated in the central nervous system. Overexpression of the human Vps13A protein in the mutant flies partly rescued apparent phenotypes. This suggests a functional conservation of human VPS13A and Drosophila Vps13. Our results demonstrate that Vps13 is essential to maintain protein homeostasis in the larval and adult Drosophila brain. Drosophila Vps13 mutants are suitable to investigate the function of Vps13 in the brain, to identify genetic enhancers and suppressors and to screen for potential therapeutic targets for Chorea-Acanthocytosis.
Topics: Animals; Brain; Drosophila; Drosophila Proteins; Homeostasis; Humans; Mutation; Nerve Tissue Proteins; Vesicular Transport Proteins
PubMed: 28107480
DOI: 10.1371/journal.pone.0170106 -
Cell Death and Differentiation Jan 2022The Drosophila IAP protein, Diap2, is a key mediator of NF-κB signalling and innate immune responses. Diap2 is required for both local immune activation, taking place...
The Drosophila IAP protein, Diap2, is a key mediator of NF-κB signalling and innate immune responses. Diap2 is required for both local immune activation, taking place in the epithelial cells of the gut and trachea, and for mounting systemic immune responses in the cells of the fat body. We have found that transgenic expression of Diap2 leads to a spontaneous induction of NF-κB target genes, inducing chronic inflammation in the Drosophila midgut, but not in the fat body. Drice is a Drosophila effector caspase known to interact and form a stable complex with Diap2. We have found that this complex formation induces its subsequent degradation, thereby regulating the amount of Diap2 driving NF-κB signalling in the intestine. Concordantly, loss of Drice activity leads to accumulation of Diap2 and to chronic intestinal inflammation. Interestingly, Drice does not interfere with pathogen-induced signalling, suggesting that it protects from immune responses induced by resident microbes. Accordingly, no inflammation was detected in transgenic Diap2 flies and Drice-mutant flies reared in axenic conditions. Hence, we show that Drice, by restraining Diap2, halts unwanted inflammatory signalling in the intestine.
Topics: Animals; Drosophila; Drosophila Proteins; Immunity, Innate; Inflammation; Inhibitor of Apoptosis Proteins; Signal Transduction
PubMed: 34262145
DOI: 10.1038/s41418-021-00832-w -
Neuron Mar 2022The nervous and endocrine systems coordinately monitor and regulate nutrient availability to maintain energy homeostasis. Sensory detection of food regulates internal...
The nervous and endocrine systems coordinately monitor and regulate nutrient availability to maintain energy homeostasis. Sensory detection of food regulates internal nutrient availability in a manner that anticipates food intake, but sensory pathways that promote anticipatory physiological changes remain unclear. Here, we identify serotonergic (5-HT) neurons as critical mediators that transform gustatory detection by sensory neurons into the activation of insulin-producing cells and enteric neurons in Drosophila. One class of 5-HT neurons responds to gustatory detection of sugars, excites insulin-producing cells, and limits consumption, suggesting that they anticipate increased nutrient levels and prevent overconsumption. A second class of 5-HT neurons responds to gustatory detection of bitter compounds and activates enteric neurons to promote gastric motility, likely to stimulate digestion and increase circulating nutrients upon food rejection. These studies demonstrate that 5-HT neurons relay acute gustatory detection to divergent pathways for longer-term stabilization of circulating nutrients.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Nutrients; Serotonergic Neurons; Taste
PubMed: 35051377
DOI: 10.1016/j.neuron.2021.12.028 -
Hereditas Dec 2006The Notch signalling pathway regulates cell-cell communication in higher eukaryotes. Cellular differentiation and tissue development relies on correct intercellular... (Review)
Review
The Notch signalling pathway regulates cell-cell communication in higher eukaryotes. Cellular differentiation and tissue development relies on correct intercellular communication, accounting for the high interest in the Notch signalling pathway. Together with mastermind and CSL (CBF-1, Suppressor of Hairless, lag-2) DNA-binding proteins, Notch forms a complex that mediates transcriptional activation of the respective target genes. This activation is strictly controlled, and deregulation causes extreme developmental defects. In Drosophila, the stringency of the control system is given by the general Notch-antagonist Hairless. Hairless assembles in a repressor complex on Notch target genes, which involves Suppressor of Hairless and two corepressors, Groucho and C-terminal binding protein. In mammals, CBF-1 recruits corepressors on its own. In addition Hairless recruits also other proteins. One example is the Pros26.4 AAA-ATPase which specifically destabilises Hairless resulting in a novel positive regulation of Notch signalling. By inhibition of Notch, Hairless not only regulates cellular differentiation but also has anti-apoptotic functions. Moreover, many genetic interactions imply a cross-talk between Hairless and the EGF-receptor pathway, which might act independently of Notch. Surprisingly, no Hairless homologue has been identified in mammals so far, despite the high degree of conservation of other components of the pathway. This discrepancy might be resolved in the future, once all components of the repressor-complex in the different species have been identified. In conclusion, Hairless is a central component of the regulation of the Notch signalling pathway in Drosophila, and is hence essential for cell differentiation and tissue development in the fly.
Topics: Alcohol Oxidoreductases; Animals; Basic Helix-Loop-Helix Transcription Factors; DNA-Binding Proteins; Down-Regulation; Drosophila Proteins; Humans; Models, Biological; Models, Genetic; Protein Isoforms; Receptors, Notch; Repressor Proteins; Ribosomes; Signal Transduction; Transcription Factors
PubMed: 17362357
DOI: 10.1111/j.2007.0018-0661.01971.x