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Author: Rebecca M. Lewis Publisher: ISBN: Category : Languages : en Pages : 96
Book Description
Sensorineural hearing loss is irreversible in all mammals, including humans, since neither hair cells nor neurons are regenerated. In contrast to mammals, non-mammalian vertebrates replace hair cells after damage. In the avian basilar papilla, hair cell injury activates neighboring supporting cells to undergo direct transdifferentiation or mitotic division, both of which contribute to regeneration of hair cells. The molecules that enable hair cell regeneration in birds are not well understood. This dissertation presents a series of experiments to evaluate whether Atoh1, a transcription factor required for hair cell development, is sufficient for hair cell differentiation in avian basilar papilla during regeneration after aminoglycoside damage and to determine if the bone morphogenetic factor BMP4, a protein required for development of auditory epithelia, inhibits Atoh1 mRNA expression and subsequent hair cell differentiation after damage. In the first study, I tracked the activity of the Atoh1 enhancer in cultured basilar papillae to determine if it is an accurate predictor of hair cell fate, and I forced expression of mouse Atoh1 in supporting cells to test the hypothesis that higher levels of Atoh1 push supporting cells to divide or transdifferentiate. This first study determined that about half of supporting cells with Atoh1 enhancer activity do not differentiate into hair cells, but relief from notch-mediated lateral inhibition or forced overexpression of Atoh1 significantly increase the likelihood that a supporting cell will differentiate as a hair cell or proliferate. In the second study, I used in situ hybridization to determine that Bmp4 mRNA is expressed in hair cells in mature chicken basilar papilla. BMP4 receptors are transcribed in supporting cells and hair cells, while inhibitor of DNA binding (Id) mRNA, a downstream effector of BMP4, is enriched in supporting cells in control tissues. Upon hair cell loss, Bmp4 mRNA expression is lost, while Atoh1 mRNA is upregulated in supporting cells. Concurrently, downstream Id effectors and receptors to BMP4 are upregulated in the area of damage. Given the observation that Bmp4 and Atoh1 have opposing expression patterns after hair cell loss, damaged basilar papillae were cultured with BMP4 protein or its inhibitor noggin after hair cell loss to determine if BMP4 antagonizes Atoh1 expression and subsequent hair cell differentiation. BMP4 eliminated Atoh1 transcripts along the length of the basilar papilla, while noggin increased Atoh1 expression. Further, BMP4 application significantly decreased the number of regenerated hair cells, while noggin application significantly increased them. These findings suggest BMP4 antagonizes hair cell regeneration by reducing Atoh1 transcripts in supporting cells, preventing them from dividing or transdifferentiating. My results are consistent with other investigators’ observations that Atoh1 is necessary for hair cell differentiation during development but additional factors such as notch ligands and BMP4 limit ATOH1’s expression. These are important considerations as investigators examine the potential for ATOH1 to stimulate auditory hair cell regeneration in humans.
Author: Rebecca M. Lewis Publisher: ISBN: Category : Languages : en Pages : 96
Book Description
Sensorineural hearing loss is irreversible in all mammals, including humans, since neither hair cells nor neurons are regenerated. In contrast to mammals, non-mammalian vertebrates replace hair cells after damage. In the avian basilar papilla, hair cell injury activates neighboring supporting cells to undergo direct transdifferentiation or mitotic division, both of which contribute to regeneration of hair cells. The molecules that enable hair cell regeneration in birds are not well understood. This dissertation presents a series of experiments to evaluate whether Atoh1, a transcription factor required for hair cell development, is sufficient for hair cell differentiation in avian basilar papilla during regeneration after aminoglycoside damage and to determine if the bone morphogenetic factor BMP4, a protein required for development of auditory epithelia, inhibits Atoh1 mRNA expression and subsequent hair cell differentiation after damage. In the first study, I tracked the activity of the Atoh1 enhancer in cultured basilar papillae to determine if it is an accurate predictor of hair cell fate, and I forced expression of mouse Atoh1 in supporting cells to test the hypothesis that higher levels of Atoh1 push supporting cells to divide or transdifferentiate. This first study determined that about half of supporting cells with Atoh1 enhancer activity do not differentiate into hair cells, but relief from notch-mediated lateral inhibition or forced overexpression of Atoh1 significantly increase the likelihood that a supporting cell will differentiate as a hair cell or proliferate. In the second study, I used in situ hybridization to determine that Bmp4 mRNA is expressed in hair cells in mature chicken basilar papilla. BMP4 receptors are transcribed in supporting cells and hair cells, while inhibitor of DNA binding (Id) mRNA, a downstream effector of BMP4, is enriched in supporting cells in control tissues. Upon hair cell loss, Bmp4 mRNA expression is lost, while Atoh1 mRNA is upregulated in supporting cells. Concurrently, downstream Id effectors and receptors to BMP4 are upregulated in the area of damage. Given the observation that Bmp4 and Atoh1 have opposing expression patterns after hair cell loss, damaged basilar papillae were cultured with BMP4 protein or its inhibitor noggin after hair cell loss to determine if BMP4 antagonizes Atoh1 expression and subsequent hair cell differentiation. BMP4 eliminated Atoh1 transcripts along the length of the basilar papilla, while noggin increased Atoh1 expression. Further, BMP4 application significantly decreased the number of regenerated hair cells, while noggin application significantly increased them. These findings suggest BMP4 antagonizes hair cell regeneration by reducing Atoh1 transcripts in supporting cells, preventing them from dividing or transdifferentiating. My results are consistent with other investigators’ observations that Atoh1 is necessary for hair cell differentiation during development but additional factors such as notch ligands and BMP4 limit ATOH1’s expression. These are important considerations as investigators examine the potential for ATOH1 to stimulate auditory hair cell regeneration in humans.
Author: Mark E. Warchol Publisher: Springer Nature ISBN: 3031206614 Category : Medical Languages : en Pages : 242
Book Description
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.
Author: Michael E. Smith Publisher: Frontiers Media SA ISBN: 2889450007 Category : Neurosciences. Biological psychiatry. Neuropsychiatry Languages : en Pages : 268
Book Description
Sensory hair cells are the specialized mechanosensory receptors found in vertebrate auditory, vestibular, and lateral line organs that transduce vibratory and acoustic stimuli into the sensations of hearing and balance. Hair cells can be damaged due to such factors as aging, ototoxic chemicals, acoustic trauma, infection, or genetic factors. Loss of these hair cells lead to deficits in hearing and balance, and in mammals, such deficits are permanent. In contrast, non-mammalian vertebrates exhibit the capability to regenerate missing hair cells. Researchers have been examining the process of hair cell death and regeneration in animal models in an attempt to find ways of either preventing hair cell loss or stimulating the production of new hair cells in mammals, with the ultimate goal of finding new therapeutics for human sensorineural hearing and balance deficits. This has led to a wide array of research on sensory hair cells- such as understanding the factors that cause hair cell loss and finding agents that protect them from damage, elucidating the cell signaling pathways activated during hair cell death, examining the genes and cellular pathways that are regulated during the process of hair cell death and regeneration, and characterizing the functional sensory loss and recovery following acoustic or ototoxic insults to the inner ear. This research has involved cell and developmental biologists, physiologists, geneticists, bioinformaticians, and otolaryngologists. In this Research Topic, we have collated reviews of the past progress of hair cell death and regeneration studies and original research articles advancing sensory hair cell death and regeneration research into the future.
Author: Richard J. Salvi Publisher: Springer Science & Business Media ISBN: 0387733647 Category : Science Languages : en Pages : 323
Book Description
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.
Author: Jason Lee Pecka Publisher: ISBN: Category : Languages : en Pages : 123
Book Description
Hearing loss due to injury of the sensory hair cells of the inner ear is largely irreversible in mammals. ATOH1, a proneural basic helix loop helix transcription factor is essential for inner ear hair cell differentiation and has garnered particular interest as a potential regeneration tool. Additionally, the transcription factors, POU4F3 and GFI1, are important in maturation and maintenance of inner ear hair cells and compel attention themselves. However, the roles of these transcription factors and their interrelationship in hair cell development and maintenance are not completely understood. In order to define a regulatory relationship between these transcription factors requires further study. We transfected a prosensory inner ear precursor cell line with these transcription factors and investigated the global transcriptome changes through microarray analysis and confirmed with quantitative RT-PCR. Furthermore, we employed a bioinformatic approach to explore the promoter regions of these genes and examined potential biological relationships through the Ingenuity Pathway Analysis software. We demonstrate that the regulatory pathways between Atoh1, Pou4f3 and Gfi1 are indirect and together comprise a larger gene regulatory network rather than a direct sequential cascade. Further evaluation revealed that these transcription factors differentially express genes classified into cell cycle and cell proliferation gene ontology categories. Pou4f3 displayed a potential to regulate multiple genes correlated with apoptosis, through which it may exhibit an important facilitatory function in hair cell maintenance. Finally, we illustrate for the first time the potential ability of Atoh1 and Gfi1 to regulate levels of certain proteins through differential regulation of the Ubc gene and cell cycle-associated binding partners.
Author: M.E. Lutman Publisher: Academic Press ISBN: 1483295168 Category : Medical Languages : en Pages : 353
Book Description
Hearing Science and Hearing Disorders focuses on the nature of the processes in the inner ear and the nervous system that mediate hearing. Organized into eight chapters, this book first discusses the nature of speech communication, the extent of hearing problems, and the pathophysiology of hearing. Four core chapters follow, in which four areas of central importance to understanding hearing disorders and their effects are covered. These areas are assessment of auditory function, the scope for technological solutions, the nature of audio-visual speech perception, and the effects of deafness upon speech production. This book will be valuable to students; to academic and professional workers concerned with hearing, speech, and their disorders; and to scientifically or medically literate people in general.
Author: Huawei Li Publisher: Springer ISBN: 9811361231 Category : Medical Languages : en Pages : 180
Book Description
This book systematically discusses the pathogenesis, prevention, and the current and potential clinical treatment of hearing loss, as well as the latest advances in hearing research. Hearing loss is a prevalent sensory disorder, which according to a 2015 World Health Organization (WHO) report affected 9% of the global population in 2015. As populations continue to age, more and more people are suffering from the condition, with 60% of those aged between 65 and 75 affected. Hearing loss seriously affects patients’ ability to work ability and quality of life, and as such deafness has become an increasingly urgent social problem around the globe. Sensorineural hearing loss is mainly caused by damage to the hair cells (HCs), and the subsequent loss of spiral ganglion neurons (SGNs). Damage to the HCs in the inner ear can result from exposure to loud noises and environmental and chemical toxins as well as genetic disorders, aging, and certain medications. This book provides ENT specialists and researchers, as well as individuals affected a comprehensive introduction to the field of hearing loss.
Author: Ruth Eatock Publisher: Springer Science & Business Media ISBN: 0387317066 Category : Science Languages : en Pages : 465
Book Description
The Springer Handbook of Auditory Research presents a series of compreh- sive and synthetic reviews of the fundamental topics in modern auditory - search. The volumes are aimed at all individuals with interests in hearing research including advanced graduate students, postdoctoral researchers, and clinical investigators. The volumes are intended to introduce new investigators to important aspects of hearing science and to help established investigators to better understand the fundamental theories and data in ?elds of hearing that they may not normally follow closely. Each volume presents a particular topic comprehensively, and each serves as a synthetic overview and guide to the literature. As such, the chapters present neither exhaustive data reviews nor original research that has not yet appeared in peer-reviewed journals. The volumes focus on topics that have developed a solid data and conceptual foundation rather than on those for which a literature is only beginning to develop. New research areas will be covered on a timely basis in the series as they begin to mature.
Author: Matthew Kelley Publisher: Springer Science & Business Media ISBN: 0387306781 Category : Science Languages : en Pages : 250
Book Description
The Springer Handbook of Auditory Research presents a series of compreh- sive and synthetic reviews of the fundamental topics in modern auditory - search. The volumes are aimed at all individuals with interests in hearing research including advanced graduate students, postdoctoral researchers, and clinical investigators. The volumes are intended to introduce new investigators to important aspects of hearing science and to help established investigators to betterunderstandthefundamentaltheoriesanddatain?eldsofhearingthatthey may not normally follow closely. Each volume presents a particular topic comprehensively, and each servesas a synthetic overview and guide to the literature. As such, the chapters present neither exhaustive data reviews nor original research that has not yet appeared in peer-reviewed journals. The volumes focus on topics that have developed a solid data and conceptual foundation rather than on those for which a literature is only beginning to develop. New research areas will be covered on a timely basis in the series as they begin to mature. Eachvolumeintheseriesconsistsofafewsubstantialchaptersonaparticular topic. In some cases, the topics will be ones of traditional interest for which there is a substantial body of data and theory, such as auditory neuroanatomy (Vol. 1) and neurophysiology (Vol. 2). Other volumes in the series deal with topics that have begun to mature more recently, suchasdevelopment,plasticity, and computational models of neural processing. In many cases, the series - itorsarejoinedbyaco-editorhavingspecialexpertiseinthetopicofthevolume.
Author: David R. Moore Publisher: Oxford University Press, USA ISBN: 0199233284 Category : Medical Languages : en Pages : 592
Book Description
Volume 1: The Ear (edited by Paul Fuchs) Volume 2: The Auditory Brain (edited by Alan Palmer and Adrian Rees) Volume 3: Hearing (edited by Chris Plack) Auditory science is one of the fastest growing areas of biomedical research. There are now around 10,000 researchers in auditory science, and ten times that number working in allied professions. This growth is attributable to several major developments: Research on the inner ear has shown that elaborate systems of mechanical, transduction and neural processes serve to improve sensitivity, sharpen frequency tuning, and modulate response of the ear to sound. Most recently, the molecular machinery underlying these phenomena has been explored and described in detail. The development, maintenance, and repair of the ear are also subjects of contemporary interest at the molecular level, as is the genetics of hearing disorders due to cochlear malfunctions.
Author: Rebecca M. Lewis
Author: Rebecca M. Lewis
Author: Mark E. Warchol
Author: Michael E. Smith
Author: Richard J. Salvi
Author: Jason Lee Pecka
Author: M.E. Lutman
Author: Huawei Li
Author: Ruth Eatock
Author: Matthew Kelley
Author: David R. Moore