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Molecular Genetics of Axial Patterning, Growth and Disease in Drosophila Eye

Molecular Genetics of Axial Patterning, Growth and Disease in Drosophila Eye PDF 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.

Molecular Genetics of Axial Patterning, Growth and Disease in the Drosophila Eye

Molecular Genetics of Axial Patterning, Growth and Disease in the Drosophila Eye PDF 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.​

Molecular Genetics of Axial Patterning, Growth and Disease in Drosophila Eye

Molecular Genetics of Axial Patterning, Growth and Disease in Drosophila Eye PDF 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.

Genetic Mechanisms Involved in Axial Patterning and Neurodegeneration in Drosophila Eye

Genetic Mechanisms Involved in Axial Patterning and Neurodegeneration in Drosophila Eye PDF 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.

Molecular Dynamics in the Developing Drosophila Eye

Molecular Dynamics in the Developing Drosophila Eye PDF Author: Daisuke Yamamoto
Publisher: Landes Bioscience
ISBN:
Category : Medical
Languages : en
Pages : 192

Book Description


Drosophila Eye Model to Study Dorso-Ventral (DV) Patterning and Neurodegenerative Disorders

Drosophila Eye Model to Study Dorso-Ventral (DV) Patterning and Neurodegenerative Disorders PDF 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.

Insights into Human Neurodegeneration: Lessons Learnt from Drosophila

Insights into Human Neurodegeneration: Lessons Learnt from Drosophila PDF 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.

Molecular mechanisms in ocular development and disease

Molecular mechanisms in ocular development and disease PDF Author: Rajalekshmy Shyam
Publisher: Frontiers Media SA
ISBN: 2832528759
Category : Science
Languages : en
Pages : 221

Book Description


Evolutionary Developmental Biology of Invertebrates 5

Evolutionary Developmental Biology of Invertebrates 5 PDF Author: Andreas Wanninger
Publisher: Springer
ISBN: 3709118689
Category : Science
Languages : en
Pages : 226

Book Description
This multi-author, six-volume work summarizes our current knowledge on the developmental biology of all major invertebrate animal phyla. The main aspects of cleavage, embryogenesis, organogenesis and gene expression are discussed in an evolutionary framework. Each chapter presents an in-depth yet concise overview of both classical and recent literature, supplemented by numerous color illustrations and micrographs of a given animal group. The largely taxon-based chapters are supplemented by essays on topical aspects relevant to modern-day EvoDevo research such as regeneration, embryos in the fossil record, homology in the age of genomics and the role of EvoDevo in the context of reconstructing evolutionary and phylogenetic scenarios. A list of open questions at the end of each chapter may serve as a source of inspiration for the next generation of EvoDevo scientists. Evolutionary Developmental Biology of Invertebrates is a must-have for any scientist, teacher or student interested in developmental and evolutionary biology as well as in general invertebrate zoology. This third volume on ecdysozoans is dedicated to the Hexapoda. Despite being the most species-rich animal clade by far, comparatively little developmental data is available for the majority of hexapods, in stark contrast to one of the best-investigated species on Earth, the fruit fly Drosophila melanogaster. Accordingly, an entire chapter is dedicated to this well-known and important model species, while the two remaining chapters summarize our current knowledge on early and late development in other hexapods.

Current Trends in the Identification and Development of Antimicrobial Agents

Current Trends in the Identification and Development of Antimicrobial Agents PDF Author: M. Amin-ul Mannan
Publisher: Bentham Science Publishers
ISBN: 9815080067
Category : Science
Languages : en
Pages : 384

Book Description
Despite an increase in life expectancy over the past 20 years, the number of novel, multidrug resistant microorganisms has also risen dramatically. To reduce the risk of reemerging infections, and limit the spread of multidrug resistant microorganisms, it is urgently necessary to develop safe and effective therapeutic countermeasures. New antimicrobial chemicals are mostly produced with the help of microorganisms, and the bulk of medications now on the market are of this type. The use of high therapeutic screening and recent developments in analytical instrumentation has allowed the researchers to identify novel antimicrobial compounds from bacteria, fungi, plants, mushrooms, algae, and other sources more quickly. The second volume of Frontiers in Antimicrobial Agents highlights the ongoing requirement for researching and creating novel antimicrobial medications. Current Trends in the Identification and Development of Antimicrobial Agents aims to bring together the expertise of notable academics to examine all facets of antimicrobial research while keeping recent advancements in perspective. Antibiotic discovery, sources of novel antimicrobial chemicals, developing and reemerging microbial infections, various elements of drug resistance, and the need for antimicrobial medications in the future are all covered in this book. It is a timely reference for anyone involved in the discovery and development of new drugs, including microbiologists, biotechnologists, pharmacologists, doctors, and researchers.

Embryogenesis Explained

Embryogenesis Explained PDF Author: Natalie K Gordon
Publisher: World Scientific
ISBN: 9814740691
Category : Science
Languages : en
Pages : 784

Book Description
The greatest mystery of life is how a single fertilized egg develops into a fully functioning, sometimes conscious multicellular organism. Embryogenesis Explained offers a new theory of how embryos build themselves, and combines simple physics with the most recent biochemical and genetic breakthroughs, based on the authors' prediction and then discovery of differentiation waves. They explain their ideas in a form accessible to the lay person and a broad spectrum of scientists and engineers. The diverse subjects of development, genetics and evolution, and their physics, are brought together to explain this major, previously unanswered scientific question of our time.As a follow up on The Hierarchical Genome, this book is a shorter but conceptually expanded work for the reader who is interested in science. It is useful as a starting point for the curious layman or the scientist or professional encountering the problem of embryogenesis without the formal biology background. There is also material useful for the seasoned biologist caught up in the new rush of information about the role of mechanics in developmental biology and cellular level mechanics in medicine.