scholarly journals Dysfunction of Torr causes a Harlequin-type ichthyosis-like phenotype in Drosophila melanogaster

2019 ◽  
Author(s):  
Y Wang ◽  
M Norum ◽  
K Oehl ◽  
Y Yang ◽  
R Zuber ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Cuticular Hydrocarbons ◽  
Abc Transporter ◽  
Water Loss ◽  
Molecular Mechanisms ◽  
Fruit Fly ◽  
Skin Surface ◽  
Barrier Formation ◽  
Pore Canals ◽  
And Function

AbstractPrevention of desiccation is a constant challenge for terrestrial organisms. Land insects have an extracellular coat, the cuticle, that plays a major role in protection against exaggerated water loss. Here, we report that the ABC transporter Torr - a human ABCA12 paralog - contributes to the waterproof barrier function of the cuticle in the fruit fly Drosophila melanogaster. We show that the reduction or elimination of Torr function provokes rapid desiccation. Torr is also involved in defining the inward barrier against xenobiotics penetration. Consistently, the amounts of cuticular hydrocarbons that are involved in cuticle impermeability decrease markedly when Torr activity is reduced. GFP-tagged Torr localises to membrane nano-protrusions within the cuticle, likely pore canals. This suggests that Torr is mediating the transport of cuticular hydrocarbons (CHC) through the pore canals to the cuticle surface. The envelope, which is the outermost cuticle layer constituting the main barrier, is unaffected in torr mutant larvae. This contrasts with the function of Snu, another ABC transporter needed for the construction of the cuticular inward and outward barriers, that nevertheless is implicated in CHC deposition. Hence, Torr and Snu have overlapping and independent roles to establish cuticular resistance against transpiration and xenobiotic penetration. The torr deficient phenotype parallels the phenotype of Harlequin ichthyosis caused by mutations in the human abca12 gene. Thus, it seems that the cellular and molecular mechanisms of lipid barrier assembly in the skin are conserved in vertebrates in invertebrates.Author SummaryAs in humans, lipids on the surface of the skin of insects protect the organism against excessive water loss and penetration of potentially harmful substances. During evolution, a greasy surface was indeed an essential trait for adaptation to life outside a watery environment. Here, we show that the membrane-gate transporter Torr is needed for the deposition of barrier lipids on the skin surface in the fruit fly Drosophila melanogaster through extracellular nano-tubes, called pore canals. In principle, the involvement of Torr parallels the scenario in humans, where the membrane-gate transporter ABCA12 is implicated in the construction of the lipid-based stratum corneum of the skin. In both cases, mutations in the genes coding for the respective transporter cause rapid water-loss and are lethal soon after birth. We conclude that the interaction between the organism and the environment obviously implies an analogous mechanism of barrier formation and function in vertebrates and invertebrates.

scholarly journals The ABC transporter Snu drives formation of the lipid-based inward and outward barrier in the skin of Drosophila

2017 ◽  
Author(s):  
Renata Zuber ◽  
Michaela Norum ◽  
Yiwen Wang ◽  
Kathrin Oehl ◽  
Davide Accardi ◽  
...  
Keyword(s):  
Abc Transporter ◽  
Complex Molecule ◽  
Skin Barrier ◽  
Fruit Fly ◽  
Second Step ◽  
Water Repellent ◽  
Pulmonary Alveoli ◽  
Barrier Formation ◽  
Step Model ◽  
Pore Canals

AbstractLipids in extracellular matrices (ECM) contribute to barrier function and stability of epithelial tissues such as the pulmonary alveoli and the skin. In insects, skin waterproofness depends on the outermost layer of the extracellular cuticle termed envelope that contains cuticulin, an unidentified water-repellent complex molecule composed of proteins, lipids and catecholamines. Based on live-imaging analyses of fruit fly larvae, we find that initially envelope units are assembled within vesicles harbouring the ABC transporter Snu and the extracellular protein Snsl. In a second step, the content of these vesicles is distributed to cuticular lipid-transporting nanotubes named pore canals and to the cuticle surface in dependence of Snu function. Consistently, the surface of snu and snsl mutant larvae is depleted from lipids and cuticulin. By consequence, these animals suffer uncontrolled water loss and penetration of xenobiotics. Our data allude to a two-step model of envelope i.e. barrier formation. The proposed mechanism in principle parallels the events occurring during differentiation of the lipid-based ECM by keratinocytes in the vertebrate skin suggesting establishment of analogous mechanisms of skin barrier formation in vertebrates and invertebrates.

scholarly journals Multilevel regulation of the glass locus during Drosophila eye development

2019 ◽  
Author(s):  
Cornelia Fritsch ◽  
F. Javier Bernardo-Garcia ◽  
Tim-Henning Humberg ◽  
Sara Miellet ◽  
Silvia Almeida ◽  
...  
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Eye Development ◽  
Fruit Fly ◽  
Protein Isoforms ◽  
Critical Feature ◽  
Reading Frame ◽  
Cis Acting ◽  
Temporal Gene Expression ◽  
And Function

ABSTRACTDevelopment of eye tissue is initiated by a conserved set of transcripton factors termed retinal determination network (RDN). In the fruit fly Drosophila melanogaster, the zinc-finger transcription factor Glass acts directly downstream of the RDN to control idendity of photoreceptor as well as non-photoreceptors cells. Tight control of spatial and temporal gene expression is a critical feature during development, cell-fate determination as well as maintainance of differentiated tissues. The molecular mechanisms that control expression of glass, however remain largely unknown. We here identify complex regulatory mechanisms controlling expression of the glass locus. All information to recapitulate glass expression are contained in a compact 5.2 kb cis-acting genomic element by combining different cell-type specific and general enhancers with repressor elements. Moreover, the immature RNA of the locus contains an alterantive small open reading frame (smORF) upstream of the actual glass translation start, resulting in a small peptide instead of the three possible glass protein isoforms. CRISPR/Cas9-based mutagenesis shows that the smORF is not required for the formation of functioning photoreceptors, but to attenuate effects of glass misexpression. Furthermore, editing the genome to generate glass loci eliminating either one or two isoforms shows that only one of the three proteins is critical for formation of functioning photoreceptors, while removing the two other isoforms did not cause defects in developmental or photoreceptor function. Our results show that eye development and function is surprisingly robust and appears buffered to targeted manipulations of critical features of the glass transcript, suggesting a strong selection pressure to allow the formation of a functioning eye.

scholarly journals Chromatin Structure and Function in Mosquitoes

2020 ◽  
Vol 11 ◽  
Author(s):  
Óscar M. Lezcano ◽  
Miriam Sánchez-Polo ◽  
José L. Ruiz ◽  
Elena Gómez-Díaz
Keyword(s):  
Drosophila Melanogaster ◽  
Regulatory Networks ◽  
Genome Structure ◽  
Nuclear Architecture ◽  
Model Organism ◽  
Fruit Fly ◽  
Model Organisms ◽  
Epigenetic Mechanisms ◽  
West Nile Fever ◽  
And Function

The principles and function of chromatin and nuclear architecture have been extensively studied in model organisms, such as Drosophila melanogaster. However, little is known about the role of these epigenetic processes in transcriptional regulation in other insects including mosquitoes, which are major disease vectors and a worldwide threat for human health. Some of these life-threatening diseases are malaria, which is caused by protozoan parasites of the genus Plasmodium and transmitted by Anopheles mosquitoes; dengue fever, which is caused by an arbovirus mainly transmitted by Aedes aegypti; and West Nile fever, which is caused by an arbovirus transmitted by Culex spp. In this contribution, we review what is known about chromatin-associated mechanisms and the 3D genome structure in various mosquito vectors, including Anopheles, Aedes, and Culex spp. We also discuss the similarities between epigenetic mechanisms in mosquitoes and the model organism Drosophila melanogaster, and advocate that the field could benefit from the cross-application of state-of-the-art functional genomic technologies that are well-developed in the fruit fly. Uncovering the mosquito regulatory genome can lead to the discovery of unique regulatory networks associated with the parasitic life-style of these insects. It is also critical to understand the molecular interactions between the vectors and the pathogens that they transmit, which could hold the key to major breakthroughs on the fight against mosquito-borne diseases. Finally, it is clear that epigenetic mechanisms controlling mosquito environmental plasticity and evolvability are also of utmost importance, particularly in the current context of globalization and climate change.

scholarly journals The Fruit Fly Drosophila melanogaster as a Model System to Study Cholesterol Metabolism and Homeostasis

Cholesterol ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Ryusuke Niwa ◽  
Yuko S. Niwa
Keyword(s):  
Drosophila Melanogaster ◽  
Steroid Hormones ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Fruit Fly ◽  
Model System ◽  
Biophysical Properties ◽  
Type C ◽  
Niemann Pick

Cholesterol has long been recognized for its versatile roles in influencing the biophysical properties of cell membranes and for serving as a precursor of steroid hormones. While many aspects of cholesterol biosynthesis are well understood, little is currently known about the molecular mechanisms of cholesterol metabolism and homeostasis. Recently, genetic approaches in the fruit fly, Drosophila melanogaster, have been successfully used for the analysis of molecular mechanisms that regulate cholesterol metabolism and homeostasis. This paper summarizes the recent studies on genes that regulate cholesterol metabolism and homeostasis, including neverland, Niemann Pick type C(NPC) disease genes, and DHR96.

scholarly journals Specification and Patterning of Drosophila Appendages

2018 ◽  
Vol 6 (3) ◽  
pp. 17 ◽  
Author(s):  
Mireya Ruiz-Losada ◽  
David Blom-Dahl ◽  
Sergio Córdoba ◽  
Carlos Estella
Keyword(s):  
Drosophila Melanogaster ◽  
Signaling Pathways ◽  
Imaginal Disc ◽  
Molecular Mechanisms ◽  
Fruit Fly ◽  
The Body ◽  
Developmental Studies ◽  
Insect Wing ◽  
Environment Exploration ◽  
Larva Development

Appendages are external projections of the body that serve the animal for locomotion, feeding, or environment exploration. The appendages of the fruit fly Drosophila melanogaster are derived from the imaginal discs, epithelial sac-like structures specified in the embryo that grow and pattern during larva development. In the last decades, genetic and developmental studies in the fruit fly have provided extensive knowledge regarding the mechanisms that direct the formation of the appendages. Importantly, many of the signaling pathways and patterning genes identified and characterized in Drosophila have similar functions during vertebrate appendage development. In this review, we will summarize the genetic and molecular mechanisms that lead to the specification of appendage primordia in the embryo and their posterior patterning during imaginal disc development. The identification of the regulatory logic underlying appendage specification in Drosophila suggests that the evolutionary origin of the insect wing is, in part, related to the development of ventral appendages.

scholarly journals Drosophila melanogaster: A Veritable Genetic Tool and in vivo Model for Human Alzheimer’s Disease

2019 ◽  
pp. 1-9
Author(s):  
Oluwatosin Imoleayo, Oyeniran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drosophila Melanogaster ◽  
Molecular Mechanisms ◽  
Fruit Fly ◽  
Human Diseases ◽  
Model Organisms ◽  
In Vivo Model ◽  
Brain Functions ◽  
Drosophila Models

The rise in the cases of neurodegenerative diseases, such as the familial forms of Alzheimer’s disease is worrisome and a burden to many societies in our ever-increasing world. Due to the complexity in the nature of the brain and spinal cord characterized by an extremely organized network of neuronal cells, there is a need to answer scientific inquiries in uncomplicated, though similar, systems. Drosophila melanogaster (fruit-fly) is a well-studied and easily managed genetic model organism used for discerning the molecular mechanisms of many human diseases. There are strong conservations of several basic biological, physiological and neurological features between D. melanogaster and mammals, as about 75% of all human disease-causing genes are considered to possess a functional homolog in the fruit-fly. The development of Drosophila models of several neurodegenerative disorders via developed transgenic technologies has presented spectacular similarities to human diseases. An advantage that the fruit-fly has over other model organisms, such as the mouse, is its comparatively brief lifespan, which allows complex inquiries about brain functions to be addressed more quickly. Furthermore, there have been steady increases in understanding the pathophysiological basis of many neurological disorders via genetic screenings with the aid of Drosophila models. This review presents a widespread summary of the fruit-fly models relevant to Alzheimer’s disease, and highlight important genetic modifiers that have been recognized using this model.

scholarly journals Drosophila melanogaster as a model for nutrient regulation of ovarian function

Reproduction ◽  
2020 ◽  
Vol 159 (2) ◽  
pp. R69-R82 ◽  
Author(s):  
Alissa Richmond Armstrong
Keyword(s):  
Drosophila Melanogaster ◽  
Nutritional Status ◽  
Egg Production ◽  
Molecular Mechanisms ◽  
Ovarian Function ◽  
Ovarian Response ◽  
Fruit Fly ◽  
Dietary Control ◽  
Nutrient Regulation ◽  
Dietary Components

Observed in a wide variety of organism, from invertebrates to mammals, nutritional status modulates the energetically costly effort of producing female gametes. Despite this long-standing link between nutrition and ovarian function, relatively little is known about the cellular and molecular mechanisms that underlie how dietary components modulate egg production. Drosophila melanogaster, with its powerful and extensive genetic tools as well as its well-characterized ovarian response to diet, has proven to be instrumental in addressing this issue. This review covers what we currently know about the dietary control of oogenesis in Drosophila and the salient features of the fruit fly that make it a model for nutritional control of ovarian function.

Reciprocal functions of the Drosophila Yellow and Ebony proteins in the development and evolution of pigment patterns

Development ◽  
2002 ◽  
Vol 129 (8) ◽  
pp. 1849-1858 ◽  
Author(s):  
Patricia J. Wittkopp ◽  
John R. True ◽  
Sean B. Carroll
Keyword(s):  
Drosophila Melanogaster ◽  
Molecular Mechanisms ◽  
Rapid Evolution ◽  
Ectopic Expression ◽  
Melanin Formation ◽  
Body Coloration ◽  
And Function ◽  
Male Specific ◽  
Development And Evolution ◽  
Pigment Patterns

Body coloration affects how animals interact with the environment. In insects, the rapid evolution of black and brown melanin patterns suggests that these are adaptive traits. The developmental and molecular mechanisms that generate these pigment patterns are largely unknown. We demonstrate that the regulation and function of the yellow and ebony genes in Drosophila melanogaster play crucial roles in this process. The Yellow protein is required to produce black melanin, and is expressed in a pattern that correlates with the distribution of this pigment. Conversely, Ebony is required to suppress some melanin formation, and is expressed in cells that will produce both melanized and non-melanized cuticle. Ectopic expression of Ebony inhibits melanin formation, but increasing Yellow expression can overcome this effect. In addition, ectopic expression of Yellow is sufficient to induce melanin formation, but only in the absence of Ebony. These results suggest that the patterns and levels of Yellow and Ebony expression together determine the pattern and intensity of melanization. Based on their functions in Drosophila melanogaster, we propose that changes in the expression of Yellow and/or Ebony may have evolved with melanin patterns. Consistent with our hypothesis, we find that Yellow and Ebony are expressed in complementary spatial patterns that correlate with the formation of an evolutionary novel, male-specific pigment pattern in Drosophila biarmipes wings. These findings provide a developmental and genetic framework for understanding the evolution of melanin patterns.

No pun intended: future directions in invertebrate glial cell migration studies

2007 ◽  
Vol 3 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Patrick Cafferty ◽  
Vanessa J. Auld
Keyword(s):  
Nervous System ◽  
Cell Migration ◽  
Glial Cell ◽  
Glial Cells ◽  
Molecular Mechanisms ◽  
System Development ◽  
Fruit Fly ◽  
Nervous System Development ◽  
Wide Range ◽  
And Function

AbstractGlial cells play a wide range of essential roles in both nervous system development and function and has been reviewed recently (Parker and Auld, 2006). Glia provide an insulating sheath, either form or direct the formation of the blood–brain barrier, contribute to ion and metabolite homeostasis and provide guidance cues. Glial function often depends on the ability of glial cells to migrate toward specific locations during nervous system development. Work in nervous system development in insects, in particular in the fruit fly Drosophila melanogaster and the tobacco hornworm Manduca sexta, has provided significant insight into the roles of glia, although the molecular mechanisms underlying glial cell migration are being determined only now. Indeed, many of the processes and mechanisms discovered in these simpler systems have direct parallels in the development of vertebrate nervous systems. In this review, we first examine the developmental contexts in which invertebrate glial cell migration has been observed, we next discuss the characterized molecules required for proper glial cell migration, and we finally discuss future goals to be addressed in the study of glial cell development.

scholarly journals Rest is Required to Learn an Appetitively-Reinforced Operant Task in Drosophila

2020 ◽  
Author(s):  
Timothy D. Wiggin ◽  
Yung-Yi Hsiao ◽  
Jeffrey B. Liu ◽  
Robert Huber ◽  
Leslie C. Griffith
Keyword(s):  
Drosophila Melanogaster ◽  
Operant Conditioning ◽  
Food Reward ◽  
Molecular Mechanisms ◽  
Genetic Model ◽  
Fruit Fly ◽  
Model Organisms ◽  
Neural Basis ◽  
Operant Task ◽  
Insight Into

ABSTRACTMaladaptive operant conditioning contributes to development of neuropsychiatric disorders. Candidate genes have been identified that contribute to this maladaptive plasticity, but the neural basis of operant conditioning in genetic model organisms remains poorly understood. The fruit fly Drosophila melanogaster is a versatile genetic model organism that readily forms operant associations with punishment stimuli. However, operant conditioning with a food reward has not been demonstrated in flies, limiting the types of neural circuits that can be studied. Here we present the first sucrose-reinforced operant conditioning paradigm for flies. Flies of both sexes walk along a Y-shaped track with reward locations at the terminus of each hallway. When flies turn in the reinforced direction at the center of the track, sucrose is presented at the end of the hallway. Only flies that rest during training show evidence of learning the reward contingency. Flies rewarded independently of their behavior do not form a learned association but have the same amount of rest as trained flies, showing that rest is not driven by learning. Optogenetically-induced rest does not promote learning, indicating that rest is not sufficient for learning the operant task. We validated the sensitivity of this assay to detect the effect of genetic manipulations by testing the classic learning mutant dunce. Dunce flies are learning impaired in the Y-Track task, indicating a likely role for cAMP in the operant coincidence detector. This novel training paradigm will provide valuable insight into the molecular mechanisms of disease and the link between sleep and learning.SIGNIFICANCE STATEMENTOperant conditioning and mental health are deeply intertwined: maladaptive conditioning contributes to many pathologies, while therapeutic operant conditioning is a frequently used tool in talk therapy. Unlike drug interventions which target molecules or mechanisms, it is not known how operant conditioning changes the brain to promote wellness or distress. To gain mechanistic insight into how this form of learning works, we developed a novel operant training task for the fruit fly Drosophila melanogaster. We made three key discoveries. First, flies are able to learn an operant task to find food reward. Second, rest during training is necessary for learning. Third, the dunce gene is necessary for both classical and operant conditioning in flies, indicating that they may share molecular mechanisms.

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