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Book Distinct Mechanisms Underlie Regeneration of Mechanosensory Hair Cells in Zebrafish

Download or read book Distinct Mechanisms Underlie Regeneration of Mechanosensory Hair Cells in Zebrafish written by Eric D. Thomas and published by . This book was released on 2018 with total page 82 pages. Available in PDF, EPUB and Kindle. Book excerpt: The mechanosensory hair cells of the inner ear mediate hearing and balance. Widespread loss of these hair cells results in severe hearing and balance deficits. Humans and other mammals are unable to regrow lost hair cells, but there are a number of other organisms, such as fish, frogs, and birds, that can. A more thorough understanding of how this hair cell regeneration occurs, at the genetic, molecular, and cellular levels, could one day allow us to target those same processes in humans and induce endogenous hair cell regeneration as a therapy for hearing and balance disorders. The zebrafish is one such organism that serves as an excellent model for hair cell regeneration. Zebrafish not only have an inner ear, but also a sensory system called the lateral line, which is comprised of clusters of hair cells arranged along the surface of the body. Lateral line hair cells are analogous to inner ear hair cells, but mediate the fish’s response to changing water flow. Previous studies have demonstrated that lateral line hair cells regenerate rapidly and completely following hair cell death, and that the surrounding support cells serve as progenitors for new hair cells. However, little is known about how progenitor function in the lateral line is regulated, and the work presented in this thesis seeks to rectify that. In Chapter 1 I provide an introduction to hair cell regeneration, with a particular focus on hair cell regeneration in the zebrafish lateral line and the inner ear. In Chapter 2, I identify genetically-distinct populations of lateral line support cells and demonstrate that they differ in their capacities to serve as hair cell progenitors. Furthermore, I show that these progenitor populations are independently regulated and that they also serve to maintain the progenitor pool within the lateral line. In Chapter 3, I develop tools to study regeneration of zebrafish inner ear hair cells and demonstrate that regeneration in the cristae occurs via transdifferentiation. Finally, in Chapter 4 I summarize my work and outline future experiments that will further elucidate our understanding of the mechanisms underlying hair cell regeneration.

Book Can You Hear Me Now  Observing Zebrafish Larvae  Danio Rerio  to Investigate Arpc1a Gene Expression with Anticipation of Hair Cell Regeneration Within the Lateral Line System

Download or read book Can You Hear Me Now Observing Zebrafish Larvae Danio Rerio to Investigate Arpc1a Gene Expression with Anticipation of Hair Cell Regeneration Within the Lateral Line System written by Lia Sage Solensten and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The sense of hearing helps organisms function within their environment. Species with biological structures for auditory function use hair cells rooted along the tympanic membrane to transmit the pressure waves from the environment into a signal recognizable to the brain, resulting in the interpretation of sound. Over time, these hair cells can face damage from a multitude of different factors including loud nose, physical trauma, and ototoxic drugs, which eventually result in hair cell loss which decreases the ability to hear. The hair cells within the ear of humans cannot regenerate causing permanent hearing loss or deafness. Zebrafish (Danio rerio) possess the ability to regrow hair cells located within their lateral line system within a matter of hours. This system helps the fish detect movement throughout the water, consisting of structures called neuromasts. The hair cells within the neuromasts are analogous to that of the hair cells found within the mammalian cochlea making zebrafish an excellent model species to study hair cell regeneration.There is little information on the mechanism behind hair cell regeneration in humans, and therefore turn to studying hair cell regeneration within the zebrafish lateral line. Scientists investigate this by identifying the location of certain genes and their expression within the zebrafish lateral line using in situ hybridization. For my senior project, I will be using in situ hybridization to examine the location of expression of the gene Arpc1a three hours post hair cell ablation. By understanding the location of the gene expression in the zebrafish, this will identify whether or not the gene plays a role in hair cell regeneration and could help contribute towards a cure to solve degenerative deafness in humans.

Book Mechanosensory Hair Cell Regeneration in the Zebrafish Lateral Line is Mitotic and Facilitated by Innervation

Download or read book Mechanosensory Hair Cell Regeneration in the Zebrafish Lateral Line is Mitotic and Facilitated by Innervation written by Scott M. Mackenzie and published by . This book was released on 2012 with total page 91 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mechanosensory hair cells in the inner ear are vulnerable to damage that can result in hearing loss and balance disorders. Exposure to excessive noise and ototoxic drugs are two of the leading causes of hair cell loss, which is irreversible in humans and other mammals. However, non-mammalian vertebrates including birds, amphibians, and fish are capable of significant hair cell regeneration that may provide insight into potential therapies for human patients. Zebrafish and other aquatic vertebrates also express hair cells in an external sensory structure called the lateral line system, which I used to study regeneration after treatment with several commonly used ototoxins. I observed that the mechanism of hair cell regeneration is remarkably consistent, existing entirely of dividing hair cell progenitors unlike the mix of proliferative regeneration and direct transdifferentiation observed in birds and amphibians. New hair cells expressed BrdU, a marker of recent cell division, and blocking proliferation with the microtubule-disrupting drug flubendazole also prevented regeneration. Although I observed no differences in the mechanism of regeneration, the type of ototoxin used to induce hair cell damage significantly affected the rate at which hair cells were replaced. For example, neomycin and gentamicin targeted exclusively mature, functional hair cells, which regenerated within 72 hours, but copper and cisplatin also killed non-sensory support cells. These support cells give rise to the dividing progenitors responsible for regeneration, delaying complete hair cell replacement by several days. I also examined how hair cell regeneration is affected by the removal of innervation, which has been previously shown to prevent tissue regeneration in the amputated amphibian limb. Although regeneration was intact in aneurogenic fish that develop hair cells without pre-existing innervation, regeneration was significantly delayed when the lateral line nerve was axotomized by laser ablation. This suggests that lateral line hair cell regeneration is at least partially nerve-dependent, though re-innervation was followed by a recovery in hair cell number. Researchers who have studied amphibian limb regeneration have implicated the role of trophic factors secreted by myelinating Schwann cells. Although my experiments indicate that Schwann cells are important for regeneration of the lateral line nerve, they do not appear to be directly responsible for mediating hair cell regeneration. A molecular mechanism that links innervation to hair cell regeneration has not been elucidated at this time, but the identification of its components might also contribute to our understanding of how proliferative regeneration is initiated in the lateral line neuromasts. The similar responses to several different ototoxins is encouraging in that it simplifies our understanding of regeneration in the lateral line and will contribute to new genetic and chemical screens for factors that prevent hair cell damage or facilitate regeneration. With an improved understanding the mechanisms underlying replacement of lateral line hair cells, this research can help develop new approaches to hair cell regeneration in humans.

Book Hair Cell Regeneration  Repair  and Protection

Download or read book Hair Cell Regeneration Repair and Protection written by Richard J. Salvi and published by Springer Science & Business Media. This book was released on 2008-03-15 with total page 323 pages. Available in PDF, EPUB and Kindle. Book excerpt: Not male pattern baldness, but the loss of sensory hair, is a very serious topic. Sensory hair cells convert sound and motion into our sense of hearing, movement, and head position. In mammals, the loss of hair cells is irreversible. Or is it? Hair cells in other vertebrates are capable of regenerating and recovering partial or complete function. This book provides a comprehensive survey of the regeneration of sensory hair cells.

Book Development of an Optogenetic Tool for Targeted Sensory Hair Cell Ablation in Zebrafish

Download or read book Development of an Optogenetic Tool for Targeted Sensory Hair Cell Ablation in Zebrafish written by Alexandria Christine Cedrone and published by . This book was released on 2022 with total page 85 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mechanosensory hair cells convert mechanical information into neuronal signals. Mutations in the genes required for hair cell function cause deafness and lead to the degeneration of sensory hair cells. Mammals are unable to regenerate these cells, leading to the permanent loss of hair cells. Research efforts are being made to stimulate hair cell regeneration in mammals and to repair genetic mutations via gene therapy to restore hearing. However, if sensory-deficient hair cells are unable to be regenerated, the effectiveness of gene therapy will be limited. To date, there are no studies examining whether mutant hair cells are able to regenerate after cell death. Other vertebrates, such as amphibians, birds, reptiles and fish, possess the ability to regenerate mechanosensory hair cells after cell death. Thus, it is of great value to investigate the genetic factors affecting the regeneration of the sensory hair cells in these species as a step towards initiating this ability in humans. This experiment uses the zebrafish model system to investigate the ability of sensory- deficient hair cells to resist ototoxic insults, and the proliferative and regenerative properties of the lateral line organ. To look at the regeneration capabilities of MET mutants, ablation methods were used to target sensory hair cells using the OptoBax system in zebrafish.

Book Wnt3 Expression in Zebrafish as a Pathway for Hair Cell Regeneration

Download or read book Wnt3 Expression in Zebrafish as a Pathway for Hair Cell Regeneration written by Stephanie Rose Blanco and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many people around the world currently suffer from hearing loss in some capacity due to the death or damage of hearing cells. Although humans are unable to regenerate hearing cells, as most mammals are unable to regenerate hair cells, non-mammal species like the zebrafish can. For my senior project, I will be conducting a research proposal that focuses on the relationship between zebrafish and their auditory senses, as well as their ability to regenerate damaged hearing cells. While the anatomy of the zebrafish species differs from humans, both species share many genetic pathways that can be used for developmental research on the inner ear. As shown through former studies, hair cell regeneration through the lateral line system works swiftly, as hair cell renewal begins to form as fast as the hair cell death occurs. One of the many factors that help to determine the number of renewed hair cells is the proliferative precursors, also known as Wnt signaling pathways and FGF signaling. While it has been determined that Wnt signaling pathways function in regulating hair cell specification, cell cycle regulation, and hair cell orientation, scientists like Aaron B. Steiner have identified many genes that express a signaling pathway of some form that can contribute to the development of hair loss treatment; one of which is the gene known as Wnt3. The purpose of this research proposal is to analyze Wnt3 signaling pathways in zebrafish to determine if Wnt3 expression can function as a pathway for hair cell regeneration. In order to analyze this candidate gene, a proposal on the experimental process of Morpholino Knockdown analysis, DiAsp staining of hair cells, Tail Fin electroporation, along with statistical analysis, will be conducted to determine the rate of hair cell regrowth in zebrafish. For this study, the hypothesis is that Wnt3 expression in zebrafish functions as a precursor for early processes of development and hair cell regeneration.

Book Zebrafish  A Model Organism for Regeneration Studies

Download or read book Zebrafish A Model Organism for Regeneration Studies written by Dr. M. Syed Ali, Ph.D and published by DARSHAN PUBLISHERS. This book was released on 2021-01-25 with total page 145 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a prelude by the authors to expose the advantages and application of Zebrafish as model organism to study various aspects of human diseases. The book starts with the introduction about the biology and lifecycle of Zebrafish that makes it suitable in a comfortable and ease way to be applied in research. The next chapter emphasizes on the methodology and application of germ-cell transplantation in this model organism. The third chapter projects the unique characteristics of this lower vertebrate organism as model system and its implementation in current scenario research for various human diseases. The next two chapters explore the genetic aspects of Zebra fish in the regeneration studies of hepatocytes and cardiomyocytes. Our goal in these chapters is to complement enormous researchers whose work deliberately exposed and reached Zebra fish to current day biologist and geneticist as a vital tool. The book finally concludes with two Appendixes that showcase the practical application of biosynthesized nanoparticle in the regeneration of Zebra fish heart and liver, carried out by our Masters students. We hope that the information presented in these chapters will definitely attract many of the budding researchers to concentrate on Zebra fish as an alternate to mice model system for their studies. We wish to express our sincere gratitude to all the contributors for their diligent effort made for the outcome of this book.

Book Hair Cell Regeneration

    Book Details:
  • Author : Mark E. Warchol
  • Publisher : Springer Nature
  • Release : 2023-04-27
  • ISBN : 3031206614
  • Pages : 242 pages

Download or read book Hair Cell Regeneration written by Mark E. Warchol and published by Springer Nature. This book was released on 2023-04-27 with total page 242 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides a detailed update on progress in the field of hair cell regeneration. This topic is of considerable interest to academicians, clinicians, and commercial entities, including students of auditory and vestibular neuroscience, audiologists, otologists, and industry, all of whom may have interest in hair cell regeneration as a potential future therapy for hearing and balance dysfunction. In 2008, Springer published a SHAR volume on this subject (Hair Cell Regeneration, Repair, and Protection, Editors Richard Salvi and Richard Fay). Since that time, there has been considerable advancement in this field.This book provides a historical perspective on the field, but the emphasis is on more "prospective" views of the various facets of regeneration research, in the hope that the volume will stimulate new projects and approaches, focusing on the limitations of current knowledge and describing promising strategies for future work. The book will include the following key features of hair cell regeneration: • Cellular and molecular control hair cell regeneration in non-mammalian species (in particular zebrafish and chickens) • Our current understanding of the capacity for hair cell replacement in mammals (rodents and humans). • Signals controlling pro-regenerative behaviors in supporting cells, the hair cell progenitors. • New techniques that have been applied to study the genetic and epigenetic regulation of hair cell regeneration in mammals and non-mammals. • Contributions of stem cells toward building new tools to explore how hair cell regeneration is controlled and toward developing cells and tissue for therapeutic transplantation. • Studies that have applied gene and drug therapy to promote regeneration in mammals.

Book Zebrafish in Development and Disease

Download or read book Zebrafish in Development and Disease written by Gokhan Dalgin and published by Frontiers Media SA. This book was released on 2019-12-06 with total page 157 pages. Available in PDF, EPUB and Kindle. Book excerpt: There are only a few vertebrate systems that can be used to model human diseases for biomedical discovery. The zebrafish model provides key advantages over existing models. Their externally developing embryos provide high-throughput non-invasive imaging, chemical screening, forward and reverse genetics, and their regeneration capacity make zebrafish a valuable system for novel discovery. Developmental studies using zebrafish has influenced discoveries in many human health-related conditions. This Research Topic covers all aspects of zebrafish studies, providing developmental mechanisms to human health conditions. The aim of the Research Topic was to foster a platform to bring all levels of zebrafish research including but not limited to development, disease, regeneration, drug screening, bioinformatics and Omics studies.

Book The Mechanosensory Lateral Line

Download or read book The Mechanosensory Lateral Line written by Sheryl Coombs and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 712 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume represents the published proceedings of an international conference on the Neurobiology and Evolution of the Mechanosensory Lateral Line System held August 31 to September 4, 1987, at the Center for Interdisciplinary Research at the University of Bielefeld, West Germany. The goal of this confer ence was to bring together researchers from all over the world to share informa tion about a major aquatic sensory system, the evolution and function of which have largely remained an enigma since the 18th century. The "lateral line" or "lateralis" system has been used as an umbrella term to describe what originally (without the aid of modern anatomical techniques) looked like a series of pits, grooves, and lines on the head and trunk of fishes and some amphibians. For at least the past 30 years, however, it has been recognized that the lateralis system comprises not one, but at least two functional classes of receptors: mechanoreceptors and electroreceptors. The relative ease with which the appropriate stimulus could be defined and measured for the electroreceptive class has resulted in an explosion of information on this submodality during the past 20 years. As a result, there is little ambiguity about the overall function of the electrosensory system, now generally regarded as an independent system in its own right. A similarly clear definition for the function of the mechanosensory lateralis system has not been as forthcoming.

Book The Role of Cadherin Fat2 in Zebrafish Hair Cell Development and Planar Cell Polarity

Download or read book The Role of Cadherin Fat2 in Zebrafish Hair Cell Development and Planar Cell Polarity written by Victoria Leigh Palfini and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Damage to the mechanosensory hair cells of the inner ear results in hearing loss and balance impairment. Although hair cell loss is permanent in humans and other mammals, nonmammalian vertebrates such as zebrafish (Danio rerio) can regenerate fully functional hair cells, making them a useful model for studying the molecular mechanisms underlying hair cell regeneration. In zebrafish, hair cells are organized into sensory organs called neuromasts. Previous studies have reported the downregulation of fat2 in the mantle cells, a type of support cell located in the neuromast that gives rise to hair cells following hair cell death. The Fat family of cadherins are involved in planar cell polarity (PCP) and regulation of cell proliferation, both of which are important for development and regeneration. In this study, I investigated Fat2's function in hair cell development and planar cell polarity through the use of immunohistochemical assays and morpholino oligonucleotide (MO)-mediated knockdown of fat2. Immunofluorescent labeling of zebrafish larvae with an antibody against Fat2 confirms that this protein localizes in the mantle cells. Although there does not appear to be a difference in the PCP of the neuromasts of MO-injected (morphant) larvae and sham-injected control larvae, Fat2 affects the hair cell populations of these two groups. Over time, the neuromasts of morphant larvae have significantly fewer hair cells than control larvae, indicating slowed cell division in morphants. These results suggest that Fat2 plays a role in cell division during development as a possible factor involved in determining the rate of mantle cell proliferation.

Book The Zebrafish  Cellular and Developmental Biology  Part B Developmental Biology

Download or read book The Zebrafish Cellular and Developmental Biology Part B Developmental Biology written by and published by Academic Press. This book was released on 2016-06-13 with total page 682 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Zebrafish: Cellular and Developmental Biology, Part B Developmental Biology, the second volume on the topic in the Methods in Cell Biology series, looks at methods for analyzing cellular and developmental biology of zebrafish. Chapters cover such topics as cell biology and developmental and neural biology. Covers sections on model systems and functional studies, imaging-based approaches, and emerging studies Chapters written by experts in the field Contains cutting-edge material on the topic of zebrafish and developments relating to their cellular and developmental biology New, two part Fourth Edition in this important volume

Book Identification and Characterization of Small Molecules that Modulate Hair Cell Development and Regeneration in the Zebrafish Lateral Line System

Download or read book Identification and Characterization of Small Molecules that Modulate Hair Cell Development and Regeneration in the Zebrafish Lateral Line System written by Wenbo Chen and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hair cells, mechanoreceptors in the ear, initiate the perception of sound. It has been demonstrated that loss of hair cells is a key factor in sensorineural hearing loss, for which there is no cure. With the ultimate goal to reverse hearing loss at the level of hair cells, 5040 chemicals from a novel compound library were evaluated for their potential modulatory effect on hair cell development and regeneration, using zebrafish lateral line neuromasts. Three enhancers and six inhibitors were confirmed by subsequent dose-response analysis. In addition, I determined that LY-411575 induced hair cell formation in zebrafish but the hair bundles were severely misorientated. Moreover, a critical window was demonstrated to be particularly important for maintaining planar cell polarity during the LY-411575 mediated hair cell regeneration process. Collectively, this research provides insight into the characterization of potential hair cell modulators.

Book Machine Learning for Zebrafish DNA Enhancer Recognition Supporting Hair Cell Regeneration

Download or read book Machine Learning for Zebrafish DNA Enhancer Recognition Supporting Hair Cell Regeneration written by Justine April West and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over 1 billion people globally are affected by some degree of hearing loss. By 2050, it is predicted that nearly 2.5 billion people will experience hearing loss and deafness. To combat hearing impairment in humans, researchers are turning towards studying mechanisms present in zebrafish for regenerative hearing to discover how they can be applied to human hearing. Using experimentally discovered genetic data gathered by researchers at the National Institutes of Health (NIH), we propose machine learning methods for efficiently improving the process of DNA enhancer discovery. Enhancers are traditionally known to play roles in development and are classically defined as non-coding DNA sequences that are located around the structural portion of a gene that regulate the transcription of genes. It is estimated that there are hundreds of thousands of enhancers in the human genome. Thus, enhancer discovery is critical to understanding how they work and how they contribute to disease. Utilizing various supervised classification and deep learning methods, when evaluating models with 5-fold cross validation, we have accurately and efficiently identified enhancer sequences and achieved an accuracy of 74.66%, 87.47%, and 89.03% for our SVM, random forest, and deep learning models respectively.

Book Transcriptome Characterization of Adult Zebrafish Inner Ear Hair Cells

Download or read book Transcriptome Characterization of Adult Zebrafish Inner Ear Hair Cells written by Cody Lincoln Barta and published by . This book was released on 2016 with total page 86 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hair cells are the vital mechanotransducer cells found in both the mammalian auditory and vestibular systems. Mammalian hair cells are non-regenerative, and thus their death leads to irreversible losses in hearing. Hair cells in zebrafish and other non-mammalian organisms such as chickens have regenerative properties, which makes them important to study. In addition to the inner ear sensory epithelia of the zebrafish, hair cells exist on the zebrafish exterior in lateral-line neuromasts. This convenient and accessible anatomy has been exploited by researchers to screen drugs for possible ototoxicity and hair cell regeneration studies. Our study focuses on the transcriptomes of the adult inner ear hair cells. Using a pou4f3 promoter-driven GAP-GFP line of transgenic adult zebrafish, hair cells were isolated from the three inner sensory epithelia: the utricle, saccule, and lagena. Two thousand GFP+ cells (hair cells) and 2000 GFP- cells (non-sensory cells in the inner ear) were individually collected by suction pipetting. RNA-seq was performed on GFP+ hair cells, and GFP- surrounding cells. The transcriptomes of the GFP+ and GFP- cells were then analyzed and compared. Using a 1 FPKM threshold, 12,444 total genes were found to be expressed in GFP+ hair cells, with 2,291 genes being differentially upregulated when being compared to the GFP- cells. A total of 13,119 total genes were found in the GFP- cells, with 1,757 genes being differentially upregulated compared to hair cells. The top ten differentially expressed genes in hair cells are anxa5a, s100s, cd164l2, pvalb9, s100t, pvalb8, si:ch73-199k24.2, atp1b2b, cabp2b, and atp1a3b. In addition, 73 zebrafish orthologs of human deafness-related genes were examined; 57 of these genes are present in adult zebrafish hair cells. The transcriptome was characterized by examining stereocilia related genes, cell cycle control genes, and ion channel and neurotransmission genes. Validation of our RNA-seq data was accomplished by RT-qPCR and literature review of published data. Our RNA-seq data of purified adult zebrafish hair cells provides an extremely valuable resource for understanding the molecular mechanisms underlying hair cell morphology, function, and pathology. This dataset also establishes a framework for future characterization of all genes expressed in hair cells.