GENETIC ANALYSIS OF ZEBRAFISH EMBRYOGENESIS
Bruce B Riley, Associate Professor
University Of Utah
75 South 2000 East
salt Lake City, Ut 84112
Grant 5F32GM014797-02 from National Institute Of General Medical Sciences IRG: BIOL
5F32GM014797-02 (1993): $9533
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Bruce B Riley
Genetic Analysis Of Inner Ear Development In Zebrafish
Bruce B Riley, Associate Professor
Texas A&m University System 400 Harvey Mitchell Parkway South College Station, Tx 77845
Grant 5R01DC003806-10 from National Institute On Deafness And Other Communication Disorders IRG: ZRG1
Abstract: This proposal seeks to elucidate mechanisms of early development of the inner ear in the zebrafish, Danio redo. The inner ear arises from a simple thickening on the surface of the embryo termed the otic placode. Our recent studies have revealed mechanisms underlying induction of the otic placode, early patterning of the otic placode, and specification of sensory hair ceils. We will follow up on these studies. Induction and early patterning of the otic placode requires Fgf signaling, and it has been suggested that another factor, Wnt8, participates in this process. Using mis-expression and loss of function techniques, we will test the relative roles of Fgf3, Fgf8, Wnt8, and Wnt8b in these processes. We will also examine the role of Fgf signaling in subsequent differentiation of sensory hair cells. The earliest known markers of otic development are members of the Pax2/5/8 family of transcription factors, which we hypothesize help mediate induction by Fgf signaling. The epistatic relationships between pax and fgf functions will be examined. Finally, we will identify additional genes acting in these pathways by screening for second site mutations that enhance the ear defects caused by mutations in pax and fgf genes. These early developmental processes, and the genetic pathways controlling them, are highly conserved. Indeed, disruption of these processes can lead to deafness in humans. Therefore, achieving a fuller understanding of how the inner ear develops could eventually lead to effective medical interventions for human deafness or other disorders of the inner ear.
Keywords: developmental neurobiology, labyrinth, neurogenesis, neurogenetics, biological signal transduction, deafness, ear hair cell, gene expression, genetic marker, point mutation, transcription factor, genetic screening, site directed mutagenesis, zebrafish
Project start date: 2003-05-01
Project end date: 2008-02-28
5R01DC003806-10 (2007): $307444
5R01DC003806-09 (2006): $316626
5R01DC003806-08 (2005): $324245
5R01DC003806-07 (2004): $324245
2R01DC003806-06 (2003): $324245
GENETIC ANALYSIS OF INNER EAR DEVELOPMENT
Bruce B Riley, Associate Professor
Biologytexas A&m University System
400 Harvey Mitchell Parkway South
college Station, Tx 77845
Grant 5R01DC003806-04 from National Institute On Deafness And Other Communication Disorders IRG: HAR
Abstract: The P.I. proposes to elucidate conserved mechanisms of vertebrate inner ear development through mutational analysis of the zebrafish, Danio rerio. Of particular interest are the molecular and cellular processes controlling the earliest stages of inner ear development, induction of the otic placode, morphogenesis of the otic vesicle, and differentiation of specific cell-types in sensory epithelia. A number of ENU-induced mutations affecting one or more of these events have been isolated and are under investigation. A variety of experiments are proposed to ascertain the means by which these mutations impede normal development of the inner ear. In addition, it is proposed to map the mutant genes with respect to molecular markers that can assist in the cloning of the affected genes. Finally, additional mutations affecting early development of the inner ear will be isolated and studied. Such systematic genetic analysis in zebrafish is likely to identify specific genes and cellular processes that operate in all vertebrates, including humans. A number of inherited and acquired diseases in humans disrupt one or both functions of the inner ear (hearing and balance) and can be quite debilitating. Determining how the inner ear develops will lead to a fuller understanding of how mature structures and functions of the inner ear are regulated. This in turn could lead to effective medical interventions to prevent, treat, or cure disorders of the inner ear
Keywords: developmental genetics, developmental neurobiology, labyrinth, neurogenetics, nonmammalian vertebrate embryology embryogenesis, gene induction /repression, genetic marker, homeobox gene, neurogenesis, point mutation animal genetic material tag, site directed mutagenesis, zebrafish
Project start date: 1998-05-01
Project end date: 2003-04-30
5R01DC003806-04 (2001): $126446
5R01DC003806-03 (2000): $121993
5R01DC003806-02 (1999): $120528
Bruce B Riley
Texas A&m University System
Project start date: 1998-05-01
Project end date: 2013-02-28
GENETIC ANALYSIS OF INNER EAR DEVELOPMENT IN ZEBRAFISH
Bruce B Riley
Texas A&m University System, 400 Harvey Mitchell Parkway South, College Station, Tx 77845
Grant 5R01DC003806-13 from National Institute On Deafness And Other Communication Disorders
Keywords: Ablation; Address; Affect; Body Tissues; Brachydanio rerio; Bypass; Cell Communication and Signaling; Cell Signaling; Cell Survival; Cell Viability; Cells; Cessation of life; Corti Cell; Danio rerio; Death; Development; Developmental Process; Down-Regulation; Down-Regulation (Physiology); Downregulation; Ear; Ear structure; Ear, Internal; Electromagnetic, Laser; Embryo; Embryonic; Epistasis; Epistasis, Genetic; Epistatic Deviation; Epithelial; Epithelium; FLR; Failure (biologic function); Ganglia; Ganglion Cysts; Ganglionic Cysts; Ganglions; Gene Targeting; Generalized Growth; Genes; Genetic Epistasis; Genetic analyses; Goals; Grant; Growth; Hair Cells; Hearing; Hearing Loss; Heat Shock; Heat-Shock Reaction; Heat-Shock Response; Hind Brain; Hour; Human; Human, General; Hypoacuses; Hypoacusis; Interaction Deviation; Intracellular Communication and Signaling; Labyrinth; Lasers; Lead; Ligands; Location; Mammalia; Mammals; Mammals, General; Mammals, Mice; Man (Taxonomy); Man, Modern; Mediating; Mesoderm; Methods and Techniques; Methods, Other; Mice; Modeling; Murine; Mus; Myxoid cyst; Natural regeneration; Nerve Cells; Nerve Unit; Nervous; Neural Cell; Neural Development; Neural Ganglion; Neurocyte; Neurons; Otic Placodes; Otic Vesicle; Pathway interactions; Pb element; Process; Proteins; Radiation, Laser; Regeneration; Relative; Relative (related person); Repression; Rhombencephalon; Role; Sensory; Sensory Hair; Signal Transduction; Signal Transduction Systems; Signaling; Site; Specific qualifier value; Specified; Staging; Structure; Supporting Cell; Surface; Targetings, Gene; Techniques; Testing; Time; Tissue Growth; Tissues; Transgenes; Transgenic Organisms; Vertebrate Animals; Vertebrates; Viral; Work; Zebra Danio; Zebra Fish; Zebrafish; biological signal transduction; cofactor; ear hair cell; failure; gene function; gene product; gene x gene interaction; genetic analysis; genetic epistases; hair cell regeneration; hearing impairment; hearing perception; heavy metal Pb; heavy metal lead; hindbrain; inner ear; insight; knock-down; loss of function; neural; neuroblast; neurodevelopment; neuronal; ontogeny; pathway; progenitor; public health relevance; regenerate; relating to nervous system; response; social role; sound perception; transgenic; vertebrata
Project start date: 1998-05-01
Project end date: 2013-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2011
PFA/PA: PA-07-070
5R01DC003806-13 (2010): $296893
Sponsored Links Excellgen http://Excellgen.com
GENETIC ANALYSIS OF ZEBRAFISH EMBRYOGENESIS
Bruce B Riley, Associate Professor
University Of Utah 75 South 2000 East Salt Lake City, Ut 84112
Grant 1F32GM014797-01 from National Institute Of General Medical Sciences IRG: BIOL
1F32GM014797-01 (1992): $22700