Andrew K Groves
Baylor College Of Medicine
Project start date: 2003-05-15
Project end date: 2015-01-31
Sponsored Links Excellgen http://Excellgen.com
Characterization Of Inner Ear Stem Cells
Andrew K Groves, Section Chief
House Ear Institute Los Angeles, Ca 90057
Grant 5R01DC006185-04 from National Institute On Deafness And Other Communication Disorders IRG: ZDC1
Abstract: The goal of this project is to characterize stem cells in the mammalian inner ear. The mammalian inner ear is unable to replace sensory hair cells lost due to damage or the long-term effects of age. Despite the considerable interest in the possibility of hair cell regeneration in mammals, virtually nothing is known concerning the identity and properties of the progenitors of sensory hair cells in the mammalian inner ear, nor whether any cells in the inner ear have the properties of stem cells. We have developed a novel cell culture system in which dissociated cells from the embryonic mouse inner ear can divide and generate hair cells, supporting cells and neurons over several weeks in culture. We will use this system to achieve the following Specific Aims. First, we will address whether single progenitor cells in the ear are multipotent and can give rise to hair cells, supporting cells and neurons, or whether they are more restricted and give rise to only a subset of these cell types. We will also test whether the developmental potential of these progenitor cells changes with time. Second, we will test whether the progenitor cells in our cultures have the extensive self-renewal capacity characteristic of true stem cells. Last, we will attempt to understand the mechanism by which Bone Morphogenetic Protein 4 (BMP-4) is able to influence multipotent progenitor cell fates in the inner ear. Our preliminary evidence suggests this growth factor causes a fivefold increase in hair cell production in cultures of inner ear epithelium. We will use both the addition of exogenous growth factors and cell-autonomous activation or repression of the BMP-4 signaling pathway to determine whether BMP-4 acts directly or indirectly, and instructively or selectively on sensory hair cell progenitors to promote hair cell differentiation.
Keywords: biological signal transduction, bone morphogenetic protein, ear hair cell, labyrinth, stem cell, cell differentiation, cell proliferation, epithelium, growth factor, hearing disorder, neuron, fluorescence microscopy, genetically modified animal, immunocytochemistry, laboratory mouse, tissue /cell culture
Project start date: 2003-05-15
Project end date: 2009-04-30
5R01DC006185-04 (2006): $355935
5R01DC006185-03 (2005): $364500
5R01DC006185-02 (2004): $364500
Grants awarded to Andrew K Groves
Andrew K Groves, Section Chief
California Institute Of Technology Office Of Sponsored Research, Mail Code 201-15 Pasadena, Ca 91125
Grant 1R03DC003630-01 from National Institute On Deafness And Other Communication Disorders IRG: ZDC1
Abstract: This small grant application seeks to study events leading to th formation of the otic placode using molecular biological techniques. The principal investigator proposes to identify the specific region of the cranial surface ectoderm that is destined to become the otic placode, and to time this event. He further plans to determine whether the presence of hindbrain tissue are necessary or sufficient to induce otic placode formation, and to time the interaction between the tissues. Finally, experiments are proposed to determi if competence to become the otic placode is specific for the placode-forming tissue or more general in surface ectoderm. These experiments are designed in chick embryos, and they require complex surgical manipulations including explanation and implantation of tissues from very young embryos and implantati of sheet barriers. In situ hybridization is the major tool for assessing the presence of the two markers, BMP-7 and Pax-2. The investigator plans to use these gene products as otic-placode-specific markers.
Keywords: cell differentiation, developmental neurobiology, ectoderm, labyrinth, biomarker, bone morphogenetic protein, embryo /fetus tissue transplantation, nervous system transplantation, rhombencephalon, chick embryo, fluorescence microscopy
Project start date: 1998-01-01
Project end date: 1998-12-31
1R03DC003630-01 (1998): $55825
Novel Method For Targeted Gene Disruption In The Ear
Andrew K Groves, Section Chief
House Ear Institute
los Angeles, Ca 90057
Grant 5R21DC004876-02 from National Institute On Deafness And Other Communication Disorders IRG: ZDC1
Abstract: This proposal is a technology-driven pilot project to develop techniques to disrupt genes specifically in the mouse inner ear. The mouse has been used successfully as a model system to understand disorders of hearing and balance, and the ability to disrupt (or "knock out") genes in mice has proved of great use in understanding gene function in the inner ear. However, studies of gene function in the inner ear using gene knockout technology are often hampered by premature lethality, or by indirect effects of gene deletion in other tissues. The ability to analyze the ear phenotype of mutant mice at all stages of development including the mature adult would be of enormous benefit to the hearing and balance research community. This proposal makes use of recently developed "Cre-Lox" technology, in which a gene flanked by LoxP DNA elements can be excised, and hence inactivated, by the Cre recombinase protein. Mating mice in which a gene of interest is flanked by LoxP sites with mice that express the Cre recombinase only in the inner ear, will excise the gene specifically in the inner ear and nowhere else. In order to develop this technology, we require a promoter that will drive gene expression only in the inner ear. We have obtained a 2.7kb promoter fragment of the ADH-4 alcohol dehydrogenase gene that directs expression in the primordium of the inner ear - the otic placode - as well as the hindbrain and neural crest. The aim of this project is to isolate fragments of the ADH-4 promoter that drive gene expression only in the otic placode and to use these fragments to construct transgenic mouse lines in which the promoter fragments drive expression of the Cre recombinase gene only in the otic placode. Many mouse lines now exist in which different genes have been flanked ("floxed") by LoxP sites. In the future, we and others will be able to mate the Cre expressing mice produced in this pilot study with such "floxed" mouse lines to disrupt genes specifically in the inner ear and to analyze the effect of gene disruption at all stages of mouse development
Keywords: gene expression, gene mutation, gene targeting, labyrinth, method development alcohol dehydrogenase, gene, genetic promoter element, integrase, recombinase animal breeding, biotechnology, histology, laboratory mouse, molecular cloning, southern blotting, transfection, transgenic animal
Project start date: 2001-05-01
Project end date: 2004-04-30
5R21DC004876-02 (2002): $74750
1R21DC004876-01 (2001): $74750
GENETIC REGULATION OF COCHLEAR DEVELOPMENT
Andrew K Groves, Associate Professor
Baylor College Of Medicine, 1 Baylor Plaza, Houston, Tx 77030-3498
Grant 2R01DC006185-05 from National Institute On Deafness And Other Communication Disorders
Abstract: The organ of Corti is a sensory specialization of the mammalian cochlea that mediates our sense of hearing. Understanding how the organ of Corti develops may shed light on the basis of certain inherited forms of deafness. It may also help attempts to regenerate the sensory cells of the cochlea in individuals where these cells have been destroyed - a common condition known as sensorineural hearing loss. The organ of Corti derives from a prosensory domain of cells running the length of the embryonic cochlear duct, but the nature of the molecular signals that induce this domain are controversial. Several studies suggest that the Notch signaling pathway induces the prosensory domain, but our own preliminary experiments using mice defective in Notch signaling do not support this idea. Instead, we suggest that Bone Morphogenetic Protein (BMP) signaling induces the prosensory domain and may also induce the non-sensory regions on either side of the organ of Corti in a concentration-dependent fashion. We do not rule out a role for Notch signaling in the developing cochlea however, as our data suggest that Notch signaling may define the boundaries of the organ of Corti by interacting with the Fringe family of Notch-modifying enzymes. The goals of this proposal are to identify the signals that induce the prosensory domain and the organ of Corti, and that correctly impart patterning information to the cochlear duct so that the right cell types are formed in the right place at the right time. We will accomplish our goals with three different approaches. First, we will use two different strains of genetically engineered mice in which the Notch signaling pathway is defective to determine whether the prosensory domain and the organ of Corti develop correctly without Notch signals. Second, we will use mice in which the BMP signaling pathway is defective, and examine the development of the cochlea. We will also test whether exposing pieces of embryonic cochlea to different concentrations of BMP can induce different cochlear cell types to differentiate. Finally, we will use genetically engineered mice that we believe will be unable to form a normal boundary between the organ of Corti and surrounding parts of the cochlea to examine the importance of this boundary in normal organ of Corti development. This proposal aims to understand how the cochlea develops in mammals. Since the cochlea is responsible for human hearing, we believe that our work will help us understand the basis of some forms of hereditary hearing loss. It may also suggest ways to re-grow damaged parts of the cochlea in individuals who have lost their hearing
Keywords: Alpha-Fucosyltransferases; Appearance; Assay; Bioassay; Biologic Assays; Biological Assay; Body Tissues; Bone Morphogenetic Proteins; Cell Communication and Signaling; Cell Death; Cell Signaling; Cells; Cochlea; Cochlear Organ; Cochlear duct; Cochlear structure; Corti Cell; Cortis Organ; Culturing, in vitro Organ; Culturing, in vitro Vertebrate, Organ; Data; Deafness; Development; Ductus Cochlearis; EC 2.4; Ear, Internal; Embryo; Embryonic; Enzymes; Family; Fucosyltransferase; Future; Genes; Genetic; Genetically Engineered Mouse; Glycoside Transferases; Goals; Hair Cells; Hair Cells, Inner; Hearing; Hearing Loss; Hearing Loss, Sensorineural; Hereditary; Human; Human, General; Hypoacuses; Hypoacusis; Image; In Vitro; Individual; Inherited; Inner Hair Cells; Intracellular Communication and Signaling; Investigators; Labyrinth; Length; Ligands; Light; MFNG; MFNG protein, human; Mammalia; Mammals; Mammals, General; Mammals, Mice; Man (Taxonomy); Man, Modern; Manic Fringe; Manic Fringe protein, human; Measures; Media, Scala; Mediating; Mediator; Mediator of Activation; Mediator of activation protein; Mice; Mice, Mutant Strains; Mice, Transgenic; Modeling; Molecular; Molecular Genetic; Molecular Genetics; Murine; Mus; Mutant Strains Mice; Natural regeneration; Nature; Nervous; Notch Signaling Pathway; Organ; Organ Culture; Organ Culture Techniques; Organ of Corti; Organ of Corti structure; Pathway interactions; Pattern; Phenotype; Photoradiation; Play; Production; Protein Family; Proteolysis and Signaling Pathway of Notch; Receptor Protein; Regeneration; Regulation; Research Personnel; Researchers; Role; Running; Scala Medias; Sensorineural Deafness; Sensorineural Hearing Loss; Sensory; Sensory Hair; Sensory Hearing Loss; Side; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; Specific qualifier value; Specified; Spiral Organ; Spiral Organ of Corti; Supporting Cell; System; System, LOINC Axis 4; Technology; Testing; Time; Tissues; To specify; Transgenic Mice; Work; assay development; base; biological signal transduction; cell type; ear hair cell; experiment; experimental research; experimental study; fng gene product; fringe gene product; fringe protein; glycosyltransferase; hearing impairment; hearing perception; human MFNG protein; imaging; inner ear; jagged-1; jagged1 protein; loss of function; manic fringe homolog (Drosophila) protein, human; member; morphogens; mouse mutant; mutant; necrocytosis; neural; notch; notch protein; notch receptors; novel; pathway; prevent; preventing; receptor; regenerate; relating to nervous system; research study; response; social role; sound perception
Relevance: This proposal aims to understand how the cochlea develops in mammals. Since the cochlea is responsible for human hearing, we believe that our work will help us understand the basis of some forms of hereditary hearing loss. It may also suggest ways to re-grow damaged parts of the cochlea in individuals who have lost their hearing
Project start date: 2003-05-15
Project end date: 2015-01-31
Budget start date: 8-FEB-2010
Budget end date: 31-JAN-2011
PFA/PA: PA-07-127
2R01DC006185-05 (2010): $458901
Characterization Of Inner Ear Stem Cells
Andrew K Groves, Section Chief
House Ear Institute Los Angeles, Ca 90057
Grant 1R01DC006185-01 from National Institute On Deafness And Other Communication Disorders IRG: ZDC1
Abstract: The goal of this project is to characterize stem cells in the mammalian inner ear. The mammalian inner ear is unable to replace sensory hair cells lost due to damage or the long-term effects of age. Despite the considerable interest in the possibility of hair cell regeneration in mammals, virtually nothing is known concerning the identity and properties of the progenitors of sensory hair cells in the mammalian inner ear, nor whether any cells in the inner ear have the properties of stem cells. We have developed a novel cell culture system in which dissociated cells from the embryonic mouse inner ear can divide and generate hair cells, supporting cells and neurons over several weeks in culture. We will use this system to achieve the following Specific Aims. First, we will address whether single progenitor cells in the ear are multipotent and can give rise to hair cells, supporting cells and neurons, or whether they are more restricted and give rise to only a subset of these cell types. We will also test whether the developmental potential of these progenitor cells changes with time. Second, we will test whether the progenitor cells in our cultures have the extensive self-renewal capacity characteristic of true stem cells. Last, we will attempt to understand the mechanism by which Bone Morphogenetic Protein 4 (BMP-4) is able to influence multipotent progenitor cell fates in the inner ear. Our preliminary evidence suggests this growth factor causes a fivefold increase in hair cell production in cultures of inner ear epithelium. We will use both the addition of exogenous growth factors and cell-autonomous activation or repression of the BMP-4 signaling pathway to determine whether BMP-4 acts directly or indirectly, and instructively or selectively on sensory hair cell progenitors to promote hair cell differentiation.
Keywords: biological signal transduction, bone morphogenetic protein, ear hair cell, labyrinth, stem cell, cell differentiation, cell proliferation, epithelium, growth factor, hearing disorder, neuron, fluorescence microscopy, immunocytochemistry, laboratory mouse, tissue /cell culture, transgenic animal
Project start date: 2003-05-15
Project end date: 2007-04-30
1R01DC006185-01 (2003): $318000
USING DROSOPHILA TO IDENTIFY HUMAN DEAFNESS GENES
Andrew K Groves, Associate Professor
Baylor College Of Medicine, 1 Baylor Plaza, Houston, Tx 77030-3498
Grant 1R21DC010987-01 from National Institute On Deafness And Other Communication Disorders
Abstract: Hearing and balance disorders are some of the most common disabilities in the United States, with 0.1% of newborns having some form of hereditary hearing loss and roughly half of all adults suffering from some degree of hearing loss by the time they reach retirement age. The causes of age-dependent hearing loss are complex, with both genetic and environmental factors playing a role. Although progress has been made understanding the genes responsible for hearing and balance disorders in children and aging adults, there is still a great need for methods to identify new genes involved in ear dysfunction and degeneration. The fruit fly Drosophila has served as an outstanding model system for understanding the genetics of development and disease. Drosophila models have been established for a number of neurodegenerative conditions, such as Alzheimer´s disease, Parkinson´s disease, Huntingdon´s disease and amyotrophic lateral sclerosis, and these models have greatly assisted our understanding of the molecular basis for neurodegeneration. Recent genetic, physiological and biophysical data suggest that despite their great separation in evolutionary time, Drosophila and mammals share many similarities in the cellular and molecular mechanisms they use to detect sound and gravity. In this exploratory R21 project we propose to develop reagents that will allow us to perform high-throughput genetic screens for hearing and gravitaxis mutants in Drosophila. The long-term goal of this project is to use Drosophila to identify genes that affect the development and function of the mammalian auditory and vestibular systems, and genes that may influence the progression of age-dependent hearing loss. In this pilot project, we will first identify genetic tools ("Flp" lines of flies) that can be used to cause mutations specifically in the hearing organ of Drosophila. Second, we will verify these Flp lines can be used to cause defects in hearing and gravity sensation by crossing them with mutant lines know to cause defects in the hearing organ of Drosophila. Finally, we will begin a pilot screen of several hundred mutagenized Drosophila lines to identify mutants with defects in hearing and gravity sensation. This project is to develop methods for identifying new genes that can cause hearing or balance defects in the fruit fly Drosophila. There is much evidence to suggest that genes involved in deafness in humans have equivalents in flies. The long term goal of this project is to use fruit flies to discover new deafness genes in humans and to understand how they affect hearing and balance in humans
Keywords: 0-11 years old; 0-6 weeks old; 21+ years old; ALS; Adult; Affect; Afferent Neurons; Age; Aging; Alzheimer; Alzheimer disease; Alzheimer sclerosis; Alzheimer syndrome; Alzheimer`s; Alzheimer`s Disease; Alzheimers Dementia; Alzheimers disease; Amyotrophic Lateral Sclerosis; Assay; Auditory; Bioassay; Biologic Assays; Biological Assay; Biological Models; Body Tissues; Child; Child Youth; Children (0-21); Chromosome 2; Chromosomes, Human, Pair 2; Collection; Complex; DNA Recombination; DNA recombination (naturally occurring); Data; Deafness; Defect; Dementia, Alzheimer Type; Dementia, Primary Senile Degenerative; Dementia, Senile; Development; Disease; Disorder; Drosophila; Drosophila genus; Dysfunction; Ear; Ear structure; Ear, Internal; Enhancer Elements; Enhancer Elements (Genetics); Enhancers; Environmental Factor; Environmental Risk Factor; Equilibrium; Esthesia; Flies; Force of Gravity; Fruit Fly, Drosophila; Functional disorder; Gehrig`s Disease; GeneHomolog; Genes; Genetic; Genetic Alteration; Genetic Change; Genetic Recombination; Genetic Screening; Genetic defect; Goals; Gravities; Hearing; Hearing Loss; Hereditary; Homolog; Homologous Gene; Homologue; Housing; Human; Human, Adult; Human, Child; Human, General; Hypoacuses; Hypoacusis; Idiopathic Parkinson Disease; Infant, Newborn; Inherited; Labyrinth; Lewy Body Parkinson Disease; Lou Gehrig Disease; Mammalia; Mammals; Mammals, General; Man (Taxonomy); Man, Modern; Mediating; Methods; Mitotic Recombination; Model System; Modeling; Models, Biologic; Molecular; Motor Neuron Disease, Amyotrophic Lateral Sclerosis; Mutation; Nerve Degeneration; Neuron Degeneration; Neurons, Afferent; Neurons, Sensory; Newborn Infant; Newborns; Notch Signaling Pathway; Organ; Paralysis Agitans; Parkinson; Parkinson Disease; Parkinson`s; Parkinson`s disease; Parkinsons disease; Physiologic; Physiological; Physiopathology; Pilot Projects; Play; Primary Parkinsonism; Primary Senile Degenerative Dementia; Proteolysis and Signaling Pathway of Notch; Reagent; Recombination; Recombination, Genetic; Retirement; Role; Senescence; Sensation; Sensory Cell Afferent Neuron; Sound; Sound - physical agent; Staining method; Stainings; Stains; System; System, LOINC Axis 4; Testing; Time; Tissues; United States; X Chromosome; adult human (21+); age dependent; age related; balance; balance function; base; cell type; children; dementia of the Alzheimer type; disability; disease/disorder; environmental risk; equilibration disorder; fly; fruit fly; genetic enhancer element; genome mutation; hearing impairment; hearing perception; imaginal disc; inner ear; mutant; neural degeneration; neurodegeneration; neuronal degeneration; newborn human (0-6 weeks); pathophysiology; pilot study; primary degenerative dementia; public health relevance; senescent; senile dementia of the Alzheimer type; social role; sound; sound perception; tool; youngster
Relevance: This project is to develop methods for identifying new genes that can cause hearing or balance defects in the fruit fly Drosophila. There is much evidence to suggest that genes involved in deafness in humans have equivalents in flies. The long term goal of this project is to use fruit flies to discover new deafness genes in humans and to understand how they affect hearing and balance in humans
Project start date: 2010-04-01
Project end date: 2012-03-31
Budget start date: 1-APR-2010
Budget end date: 31-MAR-2011
PFA/PA: PA-09-164
1R21DC010987-01 (2010): $191875
CELLULAR AND MOLECULAR MECHANISMS OF INNER EAR INDUCTION
Andrew K Groves, Section Chief
House Ear Institute Los Angeles, Ca 90057
Grant 5R01DC004675-05 from National Institute On Deafness And Other Communication Disorders IRG: ZRG1
Abstract: Adapted from applicant s ) The aim of this proposal is to study the earliest events in the development of the inner ear. One half of all cases of deafness in children are caused by inherited defects in genes that control the development or function of the inner ear. Despite the clinical significance of the inner ear, little is known about the early development of this sensory organ. The entire inner ear develops from a patch of thickened ectoderm on either side of the hindbrain called the otic placode. The otic placode is believed to be induced by signals from neighboring inducing tissues. We hypothesize that signaling molecules produced by these up-regulate of gene expression. Specific Aim 1 Induction of the otic placode is thought to be directly regulated by one or both of two candidate inducing tissues-the hind brain of the cranial paraxial mesoderm. We will test these candidate inducing tissues with responding ectoderm in a neutral tissue culture system (sufficiency experiments). Induction will be assayed using six molecular markers of the otic placode that we have recently identified. Specifc Aim 2 Two members of the fibroblast growth fibroblast growth factor (FGF) family, FGF-2 and FGF-3 have been proposed to play a role in otic placode induction, but no studies to date have rigorously tested the necessity or sufficiency of FGF signaling in this process. Accordingly, we will determine whether FGF signaling is necessary of sufficient for the induction of the otic placode by gain-and-loss of function experiment using pharmacological and dominant-negative inhibitors of FGF signaling, and application of FGF family members in vivo and in vitro. Specific Aim 3 We have identified 5 members of the chicken Dix family of homeobox-containing transcription factors, Dix -2,3,4,5 and 6. Several of these genes are expressed in the development of otic placode. We propose that Dix gene function is required to activate otic placode-specific gene expression in cranial ectoderm in response to inducing signals. We will determine whether members of the dix family of transcriptional regulators are necessary for the induction of the otic placode by creating dominantnegative constructs of these five Dix genes and expressing them in otic placode ectoderm
Keywords: developmental genetics, functional /structural genomics, gene induction /repression, gene mutation, histogenesis, labyrinth, regulatory gene, biological signal transduction, fibroblast growth factor, gene expression, homeobox gene, mesoderm, rhombencephalon, transcription factor, chick embryo, electroporation, immunocytochemistry, in situ hybridization, molecular cloning, quail, tissue /cell culture
Project start date: 2001-03-01
Project end date: 2007-02-28
5R01DC004675-05 (2005): $261625
5R01DC004675-04 (2004): $261625
5R01DC004675-03 (2003): $261625
5R01DC004675-02 (2002): $261625
Sponsored Links Excellgen http://Excellgen.com
1R01DC004675-01 (2001): $294050
CELLULAR AND MOLECULAR MECHANISMS OF OTIC PLACODE INDUCTION
Andrew K Groves, Associate Professor
Baylor College Of Medicine, 1 Baylor Plaza, Houston, Tx 77030-3498
Grant 5R01DC004675-10 from National Institute On Deafness And Other Communication Disorders
Abstract: 1 in 500 children are born with some degree of hearing loss. It is estimated that half these cases of hearing loss have a hereditary basis, some of which due to defects in the development of the inner ear. It is possible that an understanding of the earliest events in ear development may shed light on some causes of hereditary deafness. Our laboratory has chosen to study the earliest events in inner ear development - the transformation of embryonic ectoderm adjacent to the hindbrain into the otic placode, from which the entire inner ear and its associated neurons will ultimately derive. We have previously shown that signals from cranial mesoderm are necessary for otic placode induction, and that at least some of these signals are members of the Fibroblast Growth Factor (FGF) family. We have also shown that only some populations of cranial ectoderm are competent to respond to FGF signaling in this fashion, and that FGF responsiveness correlates with the expression of genes that mark the so-called "pre-placodal" region adjacent to the anterior neural plate from which all craniofacial placodes will derive. Finally, we have shown that Wnt signaling appears to act on cells that have received FGF signaling, and directs them to an otic placode, rather than an epidermal fate. This renewal seeks to build on our previous results by asking how FGF and Wnt signaling activate otic placode genes, how ectoderm cells acquire the competence to respond to FGF signaling, and how transcriptional regulators mediate the choice between otic placode and epidermis. In Specific Aim 1, we will determine whether FGF signaling induces the otic placode through the Ras/MAP kinase signaling pathway. In Specific Aim 2, we will determine whether the competence to respond to FGF signaling in otic placode induction is regulated by the presence of a functional FGF signaling pathway, or by the expression of transcription factors such as Six1, Eya2, Dachl or FoxiS in pre-placodal ectoderm. In Specific Aim 3 we will determine to what degree the Wnt and FGF signaling pathways act synergistically or independently during otic placode induction, and whether Wnt signaling directly represses epidermal fates. Finally, in Specific Aim 4, we will ask whether a novel forkhead family transcription factor, Foxi2, regulates the size of the otic placode by repressing induction of otic placode genes
Keywords: 0-11 years old; Anterior; Antimorphic mutation; Body Tissues; Cell Communication and Signaling; Cell Signaling; Cells; Cephalic; Chick Embryo; Child; Child Youth; Children (0-21); Competence; Conflict; Conflict (Psychology); Cranial; DNA Synthesis Factor; Data; Deafness; Defect; Development; Dominant Negative; Dominant-Negative Mutant; Dominant-Negative Mutation; ECGF; Ear; Ear structure; Ear, Internal; Ectoderm; Ectoderm Cell; Ectodermal Cell; Ectopic Expression; Embryo; Embryonic; Endothelial Cell Growth Factor; Epidermis; Event; FGF; FGF-R; FGFR; Family; Fibroblast Growth Factor; Fibroblast Growth Factor Receptor Family; Fibroblast Growth Factor Receptors; Fibroblast Growth Regulatory Factor; Gene Expression; Gene Family; Genes; HBGF; Head; Hearing Loss; Hereditary; Hind Brain; Human, Child; Hypoacuses; Hypoacusis; Inherited; Intracellular Communication and Signaling; Investigators; Laboratories; Labyrinth; Light; MAP Kinase Cascades; MAP Kinase Modules; MAP Kinase Signaling Cascades; MAP Kinase Signaling Pathways; Mammals, Mice; Mediating; Mediator; Mediator of Activation; Mediator of activation protein; Mesoderm; Mice; Molecular; Murine; Mus; Nerve Cells; Nerve Unit; Neural Cell; Neurocyte; Neurons; Otic Placodes; Photoradiation; Population; Programs (PT); Programs [Publication Type]; Receptors, FGF; Research Personnel; Researchers; Rhombencephalon; Role; Signal Pathway; Signal Transduction; Signal Transduction Systems; Signaling; Specific qualifier value; Specified; Testing; Tissues; To specify; base; biological signal transduction; children; craniofacial; craniofacies; hearing impairment; hindbrain; inhibitor; inhibitor/antagonist; inner ear; loss of function; member; mutant; neural plate; neuronal; novel; placodal ectoderm; programs; response; social role; transcription factor; youngster
Project start date: 2001-03-01
Project end date: 2012-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
5R01DC004675-10 (2010): $388637
5R01DC004675-09 (2009): $390506
3R01DC004675-09S1 (2009): $40000
7R01DC004675-08 (2008): $388509
2R01DC004675-06A2 (2007): $393125