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Author: Neha Gogia Publisher: ISBN: Category : Languages : en Pages : 207
Book Description
An important question in developmental biology is how any three-dimensional organ develops from single monolayer sheet of cells. In multicellular organisms, organogenesis requires axial patterning to determine Antero-Posterior (AP), Dorso-Ventral (DV), and Proximo-Distal (PD) axes. DV patterning marks first lineage restriction event during eye development, any deviation during this event during development results in defective organ formation. We have used Drosophila melanogaster (a.k.a, fruit fly) eye as our model organ as 75% of genetic machinery is conserved between fruit flies and humans and have identified defective proventriculus (dve, a Homeobox gene), an ortholog of SATB-homeobox-1 (special AT-rich sequence binding protein-1 in humans), as a new member of DV- patterning genes hierarchy. We have shown that (1) dve acts downstream of pannier (pnr, a GATA-1 transcription factor), and upstream of wingless (wg), (2) Loss-of-function (LOF) of both dve or pnr results in dorsal eye enlargements, while their Gain-of-function (GOF) suppresses the eye fate, and (3) Furthermore, Wingless (Wg, WNT homolog), downstream target of evolutionarily conserved Hippo growth regulatory pathway, acts downstream of dve in the eye, and exhibits similar eye enlargement or suppression phenotypes upon LOF or GOF. It suggests that like wg, dve also plays an important role in regulating growth. To characterize the function of dve (member of DV patterning pathway) during development, we looked for its interacting partners and found that it interacts antagonistically with Hippo signaling to regulate optimum levels of expression of their common downstream target, Wg, to specify eye versus head fate, during growth and patterning in developing eye. Additionally, GOF of SATB1 (vertebrate ortholog of dve) in the eye also resulted in Wg upregulation and eye suppression. Since GOF of hippo (hpo) triggers cell death, we tested if by blocking cell death by using p35 (anti-apoptotic) exhibits similar phenotypes. We found that eye enlargement phenotype resulting from GOF of hpo in dve domain, is not due to hpo mediated cell death, but by regulating retinal differentiation. Overall, this study presents a model that shows genetic interaction between two unrelated pathways of growth regulation and axial (DV) patterning and have significant bearing on developmental mechanisms. Another focus of this study is to employ Drosophila eye model to study Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disorder characterized by loss of upper and lower motor neurons in central nervous system with no known cure to-date. Mutations in genes like human-Fused in Sarcoma (h-FUS) or cabeza (caz) in Drosophila, have been known to cause ALS in flies. Misexpression of h-FUS-WT (Wild-Type), or FUS mutants FUS-R518K or FUS-R521C in Drosophila eye using GAL4-UAS genetic tool, triggers ALS-mediated neurodegeneration. To understand the mechanism of action, we screened for genetic modifiers and found hippo (hpo), as a genetic modifier. We next tested if this neuroprotective function is exclusive to hpo gene or is dependent on Hippo pathway. We modulated Hippo pathway in FUS-WT or mutant-FUS background and found that downregulation of Hippo pathway, exhibited significant rescue in the eye, but the exact mechanism of action was still unclear. Hippo pathway has been known to activate c-Jun-N-Terminal Kinase (JNK), which is involved in neurodegeneration and cell death. To elucidate the mechanism of action, we modulated JNK signaling in FUS or mutant-FUS background and found that downregulation of JNK signaling also rescued FUS mediated neurodegeneration in eye. This study presents a new model that explains how FUS causes neurodegeneration and has significant bearing on search for future therapeutic targets that can modify neurodegenerative behavior of ALS.
Author: Neha Gogia Publisher: ISBN: Category : Languages : en Pages : 207
Book Description
An important question in developmental biology is how any three-dimensional organ develops from single monolayer sheet of cells. In multicellular organisms, organogenesis requires axial patterning to determine Antero-Posterior (AP), Dorso-Ventral (DV), and Proximo-Distal (PD) axes. DV patterning marks first lineage restriction event during eye development, any deviation during this event during development results in defective organ formation. We have used Drosophila melanogaster (a.k.a, fruit fly) eye as our model organ as 75% of genetic machinery is conserved between fruit flies and humans and have identified defective proventriculus (dve, a Homeobox gene), an ortholog of SATB-homeobox-1 (special AT-rich sequence binding protein-1 in humans), as a new member of DV- patterning genes hierarchy. We have shown that (1) dve acts downstream of pannier (pnr, a GATA-1 transcription factor), and upstream of wingless (wg), (2) Loss-of-function (LOF) of both dve or pnr results in dorsal eye enlargements, while their Gain-of-function (GOF) suppresses the eye fate, and (3) Furthermore, Wingless (Wg, WNT homolog), downstream target of evolutionarily conserved Hippo growth regulatory pathway, acts downstream of dve in the eye, and exhibits similar eye enlargement or suppression phenotypes upon LOF or GOF. It suggests that like wg, dve also plays an important role in regulating growth. To characterize the function of dve (member of DV patterning pathway) during development, we looked for its interacting partners and found that it interacts antagonistically with Hippo signaling to regulate optimum levels of expression of their common downstream target, Wg, to specify eye versus head fate, during growth and patterning in developing eye. Additionally, GOF of SATB1 (vertebrate ortholog of dve) in the eye also resulted in Wg upregulation and eye suppression. Since GOF of hippo (hpo) triggers cell death, we tested if by blocking cell death by using p35 (anti-apoptotic) exhibits similar phenotypes. We found that eye enlargement phenotype resulting from GOF of hpo in dve domain, is not due to hpo mediated cell death, but by regulating retinal differentiation. Overall, this study presents a model that shows genetic interaction between two unrelated pathways of growth regulation and axial (DV) patterning and have significant bearing on developmental mechanisms. Another focus of this study is to employ Drosophila eye model to study Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disorder characterized by loss of upper and lower motor neurons in central nervous system with no known cure to-date. Mutations in genes like human-Fused in Sarcoma (h-FUS) or cabeza (caz) in Drosophila, have been known to cause ALS in flies. Misexpression of h-FUS-WT (Wild-Type), or FUS mutants FUS-R518K or FUS-R521C in Drosophila eye using GAL4-UAS genetic tool, triggers ALS-mediated neurodegeneration. To understand the mechanism of action, we screened for genetic modifiers and found hippo (hpo), as a genetic modifier. We next tested if this neuroprotective function is exclusive to hpo gene or is dependent on Hippo pathway. We modulated Hippo pathway in FUS-WT or mutant-FUS background and found that downregulation of Hippo pathway, exhibited significant rescue in the eye, but the exact mechanism of action was still unclear. Hippo pathway has been known to activate c-Jun-N-Terminal Kinase (JNK), which is involved in neurodegeneration and cell death. To elucidate the mechanism of action, we modulated JNK signaling in FUS or mutant-FUS background and found that downregulation of JNK signaling also rescued FUS mediated neurodegeneration in eye. This study presents a new model that explains how FUS causes neurodegeneration and has significant bearing on search for future therapeutic targets that can modify neurodegenerative behavior of ALS.
Author: Meghana Tare Publisher: ISBN: Category : Drosophila melanogaster Languages : en Pages : 240
Book Description
Complex network of genetic and molecular mechanisms governing the process of organogenesis have an important bearing on development of organisms. We are using an established model of Drosophila melanogaster commonly referred to as fruit fly in order to understand these mechanisms. We have used Drosophila eye to discern genetic hierarchy controlling the (i) event of axial patterning, and (ii) to study neurodegeneration in the developing eye. Axial patterning involves generation of dorsal-ventral (DV), anterior-posterior (AP) and proximal-distal (PD) axes in the organ primordium and is considered crucial for transformation of monolayer epithelium into a three dimensional organ. Any abnormalities in expression patterns of axial patterning genes may result in complete loss of organ. Drosophila eye develops from a default ventral state conferred by expression of genes Lobe (L) and Serrate (Ser). It has been found that antagonistic interaction of dorsal and ventral genes helps generation of midline or the equator which is essential for growth and differentiation of the eye field. Loss-of-function of L/Ser results in complete or loss-of-ventral eye depending on time axis involved. In a genetic modifier screen performed for search for modifiers of L mutant phenotypes, an E3 ubiquitin ligase, Cullin-4 (Cul-4) and GATA-1 transcription factor Pannier (Pnr) were identified. In the current study, we have characterized Cul-4, in promoting cell survival in the ventral domain of developing eye via downregulation of Wingless (Wg) signaling. Cul-4 also regulates JNK signaling to prevent cell death in the developing eye. We thus place the Cul-4 in the hierarchy of ventral genes involved in eye development.We also present the role of GATA-1 transcription factor Pnr in defining the dorsal eye margin boundary by suppressing the eye fate. Pnr downregulates retinal determination gene machinery via zinc finger transcription factor teashirt (tsh). We thus provide a novel mechanism involved in defining dorsal margins of the eye during early stages of organogenesis and an eye suppression function, as a late role of pnr in the developing eye. Identification and characterization of these genes in the dorsal and ventral domains of the eye may help enrich our understanding of the genetic hierarchy and the complex interactions of genes involved in axial patterning in the eye during organogenesis. Since the genetic machinery is highly conserved from flies to humans, these studies will have direct implications on higher vertebrates as well. Other than patterning and growth studies, Drosophila eye has been widely used to study genetic and molecular basis of neurodegeneration. A part of current study is to test the mechanisms involved in the neuronal cell death caused during the course of Alzheimer's disease (AD). AD is caused due to accumulation of Aß-42 peptide which is a product formed because of incorrect cleavage of Amyloid Precursor Protein (APP). Accumulation of Aß-42 results in formation of amyloid plaques which eventually results into stress and the neuronal cell death. We have found that JNK signaling pathway is induced upon Aß-42 accumulation and causes cell death of the neurons in the brain. Our study provides a new mechanistic insight from the perspective of identifying the new targets of AD neuropathy.
Author: Amit Singh Publisher: Springer Science & Business Media ISBN: 1461482321 Category : Medical Languages : en Pages : 375
Book Description
Undoubtedly, Drosophila melanogaster, fruit fly, has proved to be one of the most popular invertebrate model organisms, and the work horse for modern day biologists. Drosophila, a highly versatile model with a genetic legacy of more than a century, provides powerful genetic, cellular, biochemical and molecular biology tools to address many questions extending from basic biology to human diseases. One of the most important questions in biology focuses on how does a multi-cellular organism develop from a single-celled embryo. The discovery of the genes responsible for pattern formation has helped refine this question, and led to other questions, such as the role of various genetics and cell biological pathways in regulating the crucial process of pattern formation and growth during organogenesis. Drosophila eye model has been extensively used to study molecular genetic mechanisms involved in patterning and growth. Since the genetic machinery involved in the Drosophila eye is similar to humans, it has been used to model human diseases and homology to eyes in other taxa. This book will discuss molecular genetic mechanisms of pattern formation, mutations in axial patterning, Genetic regulation of growth in Drosophila eye, and more. There have been no titles in the past ten years covering this topic, thus an update is urgently needed.
Author: Farzana Khan Perveen Publisher: BoD – Books on Demand ISBN: 9535138537 Category : Technology & Engineering Languages : en Pages : 270
Book Description
This book contains 12 chapters divided into two sections. Section 1 is "Drosophila - Model for Genetics." It covers introduction, chromosomal polymorphism, polytene chromosomes, chromosomal inversion, chromosomal evolution, cell cycle regulators in meiosis and nongenetic transgenerational inheritance in Drosophila. It also includes ecological genetics, wild-type strains, morphometric analysis, cytostatics, frequencies of early and late embryonic lethals (EEL and LEL) and mosaic imaginal discs of Drosophila for genetic analysis in biomedical research. Section 2 is "Drosophila - Model for Therapeutics." It explains Drosophila as model for human diseases, neurodegeneration, heart-kidney metabolic disorders, cancer, pathophysiology of Parkinson's disease, dopamine, neuroprotective therapeutics, mitochondrial dysfunction and translational research. It also covers Drosophila role in ubiquitin-carboxyl-terminal hydrolase-L1 (UCH-L1) protein, eye development, anti-dUCH antibody, neuropathy target esterase (NTE), organophosphorous compound-induced delayed neuropathy (OPIDN) and hereditary spastic paraplegia (HSP). It also includes substrate specificities, kinetic parameters of recombinant glutathione S-transferases E6 and E7 (DmGSTE6 and DmGSTE7), detoxification and insecticidal resistance and antiviral immunity in Drosophila.
Author: Amit Singh Publisher: Springer Nature ISBN: 3030422461 Category : Medical Languages : en Pages : 368
Book Description
Drosophila melanogaster (fruit fly) is a highly versatile model with a genetic legacy of more than a century. It provides powerful genetic, cellular, biochemical and molecular biology tools to address many questions extending from basic biology to human diseases. One of the most important questions in biology is how a multi-cellular organism develops from a single-celled embryo. The discovery of the genes responsible for pattern formation has helped refine this question and has led to other questions, such as the role of various genetic and cell biological pathways in regulating the process of pattern formation and growth during organogenesis. The Drosophila eye model has been extensively used to study molecular genetic mechanisms involved in patterning and growth. Since the genetic machinery involved in the Drosophila eye is similar to humans, it has been used to model human diseases and homology to eyes in other taxa. This updated second edition covers current progress in the study of molecular genetic mechanisms of pattern formation, mutations in axial patterning, genetic regulation of growth, and more using the Drosophila eye as a model.
Author: Marek Mlodzik Publisher: Elsevier ISBN: 0080458610 Category : Science Languages : en Pages : 183
Book Description
Cellular polarization is key to all cellular functions. Our perceptions, which are derived from our senses, depend on the proper cellular polarization of our sense organs, such as the eyes or ears. Much of this book examines the different aspects in cellular polarization and its researched role in the Drosophila, where the first planar cellular polarity (PCP) gene was discovered over 20 years ago. Topics also include: From flies to man: how we are polarized, Marking an embryo work, Cellular polarization at its functional best, Hearing and seeing your environment, and From a cell to an organ. This series represents timely issues in developmental biology. It provides annual reviews of selected topics, written from the perspectives of leading investigators in the field of development. * Presents many various organisms such as flies, fish, frogs and mice * Offers over 40 exceptional illustrations * First of its kind to include new data and detailed models on cell planar polarization
Author: Nelson R Cabej Publisher: Academic Press ISBN: 0128143126 Category : Science Languages : en Pages : 258
Book Description
Epigenetic Mechanisms of the Cambrian Explosion provides readers with a basic biological knowledge and epigenetic explanation of the biological puzzle of the Cambrian explosion, the unprecedented rapid diversification of animals that began 542 million years ago. During an evolutionarily instant of ~10 million years, which represents only 0.3% of the time of existence of life on Earth, or less than 2% of the time of existence of metazoans, all of the 30 extant body plans, major animal groups (phyla) and several extinct groups appeared. The work helps address this phenomena and tries to answer remaining questions for evolutionary biology, epigenetics, and scientific researchers. The book recognizes and presents objective representations of alternative theories for epigenetic evolution in this period, with the author drawing on his epigenetic theory of evolution to explain the causal basis of the Cambrian explosion. Both empirical evidence and theoretical arguments are presented in support of this thought-provoking epigenetic theory. Explains the Cambrian explosion from an entirely epigenetic view Takes a causal rather than descriptive approach to the phenomenon Allows for a broad readership, including those with only a basic biological knowledge, while maintaining scientific rigor
Author: Mousumi Mutsuddi Publisher: Springer Nature ISBN: 981132218X Category : Medical Languages : en Pages : 470
Book Description
This book is aimed at generating an updated reservoir of scientific endeavors undertaken to unravel the complicated yet intriguing topic of neurodegeneration. Scientists from Europe, USA and India who are experts in the field of neurodegenerative diseases have contributed to this book. This book will help readers gain insight into the recent knowledge obtained from Drosophila model, in understanding the molecular mechanisms underlying neurodegenerative disorders and also unravel novel scopes for therapeutic interventions. Different methodologies available to create humanized fly models that faithfully reflects the pathogenicities associated with particular disorders have been described here. It also includes information on the exciting area of neural stem cells. A brief discussion on neurofibrillary tangles, precedes the elaborate description of lessons learnt from Drosophila about Alzheimer's, Parkinson’s, Spinomuscular Atrophy, Huntington’s diseases, RNA expansion disorders and Hereditary Spastic Paraplegia. We have concluded the book with the use of Drosophila for identifying pharmacological therapies for neurodegenerative disorders. The wide range of topics covered here will not only be relevant for beginners who are new to the concept of the extensive utility of Drosophila as a model to study human disorders; but will also be an important contribution to the scientific community, with an insight into the paradigm shift in our understanding of neurodegenerative disorders. Completed with informative tables and communicative illustrations this book will keep the readers glued and intrigued. We have comprehensively anthologized the lessons learnt on neurodegeneration from Drosophila and have thus provided an insight into the multidimensional aspects of pathogenicities of majority of the neurodegenerative disorders.
Author: Rita Sattler Publisher: Springer ISBN: 331989689X Category : Medical Languages : en Pages : 310
Book Description
It has become evident over the last years that abnormalities in RNA processing play a fundamental part in the pathogenesis of neurodegenerative diseases. Cellular viability depends on proper regulation of RNA metabolism and subsequent protein synthesis, which requires the interplay of many processes including transcription, pre--‐mRNA splicing, mRNA editing as well as mRNA stability, transport and translation. Dysfunction in any of these processes, often caused by mutations in the coding and non--‐ coding RNAs, can be very destructive to the cellular environment and consequently impair neural viability. The result of this RNA toxicity can lead to a toxic gain of function or a loss of function, depending on the nature of the mutation. For example, in repeat expansion disorders, such as the newly discovered hexanucleotide repeat expansion in theC9orf72 gene found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a toxic gain of function leads to the formation of RNA foci and the sequestration of RNA binding proteins (RBPs). This in return leads to a loss of function of those RBPs, which is hypothesized to play a significant part in the disease progression of ALS and FTD. Other toxicities arising from repeat expansions are the formation of RNA foci, bi--‐directional transcription and production of repeat associated non--‐ATG (RAN) translation products. This book will touch upon most of these disease mechanisms triggered by aberrant RNA metabolism and will therefore provide a broad perspective of the role of RNA processing and its dysfunction in a variety of neurodegenerative disorders, including ALS, FTD, Alzheimer’s disease, Huntington’s disease, spinal muscular atrophy, myotonic dystrophy and ataxias. The proposed authors are leading scientists in the field and are expected to not only discuss their own work, but to be inclusive of historic as well as late breaking discoveries. The compiled chapters will therefore provide a unique collection of novel studies and hypotheses aimed to describe the consequences of altered RNA processing events and its newest molecular players and pathways.
Author: Hans Liljenström Publisher: Elsevier ISBN: 0080554636 Category : Mathematics Languages : en Pages : 349
Book Description
It was not long ago when the consciousness was not considered a problem for science. However, this has now changed and the problem of consciousness is considered the greatest challenge to science. In the last decade, a great number of books and articles have been published in the field, but very few have focused on the how consciousness evolves and develops, and what characterizes the transitions between different conscious states, in animals and humans. This book addresses these questions. Renowned researchers from different fields of science (including neurobiology, evolutionary biology, ethology, cognitive science, computational neuroscience and philosophy) contribute with their results and theories in this book, making it a unique collection of the state-of-the-art of this young field of consciousness studies. First book on the topic Focus on different levels of consciousness, including: Evolutionary, developmental, and functional Highly interdisciplinary
Author: Neha Gogia
Author: Neha Gogia
Author: Meghana Tare
Author: Amit Singh
Author: Farzana Khan Perveen
Author: Amit Singh
Author: Marek Mlodzik
Author: Nelson R Cabej
Author: Mousumi Mutsuddi
Author: Rita Sattler
Author: Hans Liljenström