FGF SIGNALING DURING CRANIAL PLACODE DEVELOPMENT
Alex Nechiporuk
University Of Washington Office Of Sponsored Programs Seattle, Wa 98105
Grant 5F32HD047103-03 from National Institute Of Child Health And Human Development IRG: ZRG1
Abstract: In vertebrates, cranial sensory ganglia, including trigeminal, epibranchial (EB), and lateral line (LL) ganglia, derive from two sources neural crest and ectodermal placodes. The proper development of cranial nerves is essential for the formation of cranial sensory systems such as vision, smell, hearing, somatosensation, and taste. Despite their importance, very little is known about molecular mechanisms that govern the development of specific cranial placodes. Our preliminary data indicate that fibroblast growth factor (Fgf) signaling is required for the formation of EB and LL placodes. We will take advantage of advanced genetic tools in zebrafish to define roles for Fgf signaling during formation of EB and LL placodes. First, we will establish temporal and special requirements for Fgf signaling using pharmacologic Fgf-receptor inhibitor and inducible, dominant-negative Fgf-receptor transgenic zebrafish. Second, we will determine whether Fgf signaling is required during early steps of cranial placodes formation (placode induction and cell migration) or during later steps (proliferation and survival of neurons). Finally, we will identify specific Fgf ligands that are required for the formation of EB and LL line placodes.
Keywords: cranial nerve, developmental neurobiology, fibroblast growth factor, neurogenesis, nonmammalian vertebrate embryology, cell migration, developmental genetics, growth factor receptor, neurogenetics, genetically modified animal, postdoctoral investigator, zebrafish
Project start date: 2004-05-01
Project end date: 2007-04-30
5F32HD047103-03 (2006): $50428
Sponsored Links Excellgen http://Excellgen.com
FGF SIGNALING DURING CRANIAL PLACODE DEVELOPMENT
Alex Nechiporuk
University Of Washington Office Of Sponsored Programs Seattle, Wa 98105
Grant 5F32HD047103-02 from National Institute Of Child Health And Human Development IRG: ZRG1
Abstract: In vertebrates, cranial sensory ganglia, including trigeminal, epibranchial (EB), and lateral line (LL) ganglia, derive from two sources neural crest and ectodermal placodes. The proper development of cranial nerves is essential for the formation of cranial sensory systems such as vision, smell, hearing, somatosensation, and taste. Despite their importance, very little is known about molecular mechanisms that govern the development of specific cranial placodes. Our preliminary data indicate that fibroblast growth factor (Fgf) signaling is required for the formation of EB and LL placodes. We will take advantage of advanced genetic tools in zebrafish to define roles for Fgf signaling during formation of EB and LL placodes. First, we will establish temporal and special requirements for Fgf signaling using pharmacologic Fgf-receptor inhibitor and inducible, dominant-negative Fgf-receptor transgenic zebrafish. Second, we will determine whether Fgf signaling is required during early steps of cranial placodes formation (placode induction and cell migration) or during later steps (proliferation and survival of neurons). Finally, we will identify specific Fgf ligands that are required for the formation of EB and LL line placodes.
Keywords: cranial nerve, developmental neurobiology, fibroblast growth factor, neurogenesis, nonmammalian vertebrate embryology, cell migration, developmental genetics, growth factor receptor, neurogenetics, genetically modified animal, postdoctoral investigator, zebrafish
Project start date: 2004-05-01
Project end date: 2007-04-30
5F32HD047103-02 (2005): $48296
Grants awarded to Alex Nechiporuk
DEVELOPMENT OF EPIBRANCHIAL PLACODES AND GANGLIA IN ZEBRAFISH
Alex Nechiporuk, Assistant Professor
Oregon Health And Science University, 3181 Sw Sam Jackson Pk Rd, Portland, Or 97239-3098
Grant 3R00HD055303-04S1 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: Research project In vertebrates, sensory neurons of the parasympathetic epibranchial (EB) ganglia derived from ectodermal placodes are essential for the formation of cranial sensory systems such as smell, somatosensation, and taste. Despite their importance, very little is known about molecular mechanisms that govern various developmental aspects of EB placodes and ganglia. The overall goals of this proposal are 1) To define the cellular and molecular mechanisms that are responsible for segregation of the early EB precursors from the common placodal field. 2) To take advantage of advanced genetic tools in zebrafish in order to identify novel genes responsible for EB placode and ganglia development. Candidate I have a long-standing interest in developmental biology. One unifying theme during my graduate and postodoctoral research was to address the question how naive progenitor cells segregate to give rise to diverse cell types that eventually form an organ. The importance of this question is even more profound when applied to a vertebrate nervous system, where hundreds of cell types exist. During the K99 part of this proposal, I will study how Fgf signaling regulates segregation of EB placode precursors from a common progenitor field. This work is a direct extension of my current NRSA fellowship to study roles of Fgf signaling during EB placode development. I plan to continue developing technology that will assist me in studying cranial placodes and ganglia, including generation and testing of zebrafish transgenic lines, which will greatly facilitate the mutagenesis screen proposed during the ROO phase. Following my postdoctoral work, I plan to establish an independent basic research program in an academic setting. I expect that practical and theoretical knowledge gained during the K99 part of the training will help me to jump-start my own independent studies and will also allow me to venture into new aspects of zebrafish biology. Relevance Sensory component of the parasympathetic nervous system has been implicated in many human disorders, including chronic obstructive pulmonary disease, migraines, bladder overactivity, and erectile dysfunction. Dysfunction in the afferent branch of the parasympathetic system could lead to congestive heart failure or arrhythmia. Thus, uncovering genes that specify EB placodes and ganglia should provide better understanding for the mechanisms underlying these disorders
Keywords: Ablation; Address; Afferent Neurons; Arrhythmia; Basic Research; Basic Science; Biology; Bladder; Brachydanio rerio; COAD; COPD; Cardiac; Cardiac Arrhythmia; Cardiac Failure Congestive; Cell Communication and Signaling; Cell Lineage; Cell Signaling; Cells; Cephalic; Chromosome Mapping; Chronic Obstructive Airway Disease; Chronic Obstructive Lung Disease; Congestive Heart Failure; Cranial; Cranial Nerve I; Cranial Nerve Is; Danio rerio; Data; Development; Developmental Biology; Disease; Disorder; Dysfunction; Ectoderm; Embryo; Embryonic; Erectile dysfunction; Extracellular Signal-Regulated Kinase Gene; Fellowship; Filopodia; First Cranial Nerve; Functional disorder; Ganglia; Ganglion Cysts; Ganglionic Cysts; Ganglions; Gene Localization; Gene Mapping; Gene Mapping, Total Human and Non-Human; Generations; Genes; Genetic; Genetic Alteration; Genetic Change; Genetic Screening; Genetic defect; Genetics, Gene Mapping; Genetics-Mutagenesis; Goals; Gustation; Headache, Migraine; Heart Arrhythmias; Heart Decompensation; Heart Failure, Congestive; Human; Human, General; Intracellular Communication and Signaling; Ischemia; Knowledge; Laboratories; Lead; Lesion; Life; Linkage Mapping; MAP Kinase Gene; MAPK; Man (Taxonomy); Man, Modern; Maps; Methods and Techniques; Methods, Other; Migraine; Mitogen-Activated Protein Kinase Gene; Molecular; Molecular Biology, Mutagenesis; Mother Cells; Mutagenesis; Mutate; Mutation; Myxoid cyst; NRSA; NRVS-SYS; National Research Service Awards; Nature; Nerve Cells; Nerve Unit; Nervous System; Nervous system structure; Neural Cell; Neural Crest; Neural Ganglion; Neurocyte; Neurologic Body System; Neurologic Organ System; Neurons; Neurons, Afferent; Neurons, Sensory; Olfaction; Olfactions; Olfactory Nerve; Organ; Parasympathetic Nervous System; Pb element; Phase; Physiopathology; Progenitor Cells; Programs (PT); Programs [Publication Type]; Pulmonary Disease, Chronic Obstructive; R01 Mechanism; R01 Program; RPG; Racial Segregation; Research; Research Grants; Research Project Grants; Research Projects; Research Projects, R-Series; Role; Screening procedure; Sensory; Sensory Cell Afferent Neuron; Signal Transduction; Signal Transduction Systems; Signaling; Smell; Smell Perception; Specific qualifier value; Specified; Stem cells; System; System, LOINC Axis 4; Taste; Taste Perception; Techniques; Technology; Testing; Training; Transgenic Organisms; Urinary System, Bladder; Vertebrate Animals; Vertebrates; Work; Zebra Danio; Zebra Fish; Zebrafish; base; biological signal transduction; cell type; disease/disorder; experiment; experimental research; experimental study; genetic mapping; genome mutation; heavy metal Pb; heavy metal lead; innervation; interest; migration; mutant; nerve supply; neuronal; novel; pathophysiology; progenitor; programs; research study; screening; screenings; segregation; sensory system; social role; tool; transgenic; urinary bladder; vertebrata
Project start date: 2009-09-30
Project end date: 2010-09-29
Budget start date: 30-SEP-2009
Budget end date: 29-SEP-2010
PFA/PA: PA-07-297
3R00HD055303-04S1 (2009): $42085
1K99HD055303-01 (2007): $90000
FGF SIGNALING DURING CRANIAL PLACODE DEVELOPMENT
Alex Nechiporuk
University Of Washington Office Of Sponsored Programs Seattle, Wa 98105
Grant 1F32HD047103-01 from National Institute Of Child Health And Human Development IRG: ZRG1
Abstract: In vertebrates, cranial sensory ganglia, including trigeminal, epibranchial (EB), and lateral line (LL) ganglia, derive from two sources neural crest and ectodermal placodes. The proper development of cranial nerves is essential for the formation of cranial sensory systems such as vision, smell, hearing, somatosensation, and taste. Despite their importance, very little is known about molecular mechanisms that govern the development of specific cranial placodes. Our preliminary data indicate that fibroblast growth factor (Fgf) signaling is required for the formation of EB and LL placodes. We will take advantage of advanced genetic tools in zebrafish to define roles for Fgf signaling during formation of EB and LL placodes. First, we will establish temporal and special requirements for Fgf signaling using pharmacologic Fgf-receptor inhibitor and inducible, dominant-negative Fgf-receptor transgenic zebrafish. Second, we will determine whether Fgf signaling is required during early steps of cranial placodes formation (placode induction and cell migration) or during later steps (proliferation and survival of neurons). Finally, we will identify specific Fgf ligands that are required for the formation of EB and LL line placodes.
Keywords: cranial nerve, developmental neurobiology, fibroblast growth factor, neurogenesis, nonmammalian vertebrate embryology, cell migration, developmental genetics, growth factor receptor, neurogenetics, genetically modified animal, postdoctoral investigator, zebrafish
Project start date: 2004-05-01
Project end date: 2007-04-30
1F32HD047103-01 (2004): $42976
DEVELOPMENT OF EPIBRANCHIAL PLACODES AND GANGLIA IN ZEBRAFISH
Alex Nechiporuk, Assistant Professor
Oregon Health And Science University, 3181 Sw Sam Jackson Pk Rd, Portland, Or 97239-3098
Grant 5R00HD055303-05 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Keywords: Ablation; Address; Afferent Neurons; Arrhythmia; Basic Research; Basic Science; Biology; Bladder; Brachydanio rerio; COAD; COPD; Cardiac; Cardiac Arrhythmia; Cardiac Failure Congestive; Cell Communication and Signaling; Cell Lineage; Cell Signaling; Cells; Cephalic; Chromosome Mapping; Chronic Obstructive Airway Disease; Chronic Obstructive Lung Disease; Congestive Heart Failure; Cranial; Cranial Nerve I; Cranial Nerve Is; Danio rerio; Data; Development; Developmental Biology; Disease; Disorder; Dysfunction; Ectoderm; Embryo; Embryonic; Erectile dysfunction; Extracellular Signal-Regulated Kinase Gene; Fellowship; Filopodia; First Cranial Nerve; Functional disorder; Ganglia; Ganglion Cysts; Ganglionic Cysts; Ganglions; Gene Localization; Gene Mapping; Gene Mapping, Total Human and Non-Human; Generations; Genes; Genetic; Genetic Alteration; Genetic Change; Genetic Screening; Genetic defect; Genetics, Gene Mapping; Genetics-Mutagenesis; Goals; Gustation; Headache, Migraine; Heart Arrhythmias; Heart Decompensation; Heart Failure, Congestive; Human; Human, General; Intracellular Communication and Signaling; Ischemia; Knowledge; Laboratories; Lead; Lesion; Life; Linkage Mapping; MAP Kinase Gene; MAPK; Man (Taxonomy); Man, Modern; Maps; Methods and Techniques; Methods, Other; Migraine; Mitogen-Activated Protein Kinase Gene; Molecular; Molecular Biology, Mutagenesis; Mother Cells; Mutagenesis; Mutate; Mutation; Myxoid cyst; NRSA; NRVS-SYS; National Research Service Awards; Nature; Nerve Cells; Nerve Unit; Nervous System; Nervous system structure; Neural Cell; Neural Crest; Neural Ganglion; Neurocyte; Neurologic Body System; Neurologic Organ System; Neurons; Neurons, Afferent; Neurons, Sensory; Olfaction; Olfactions; Olfactory Nerve; Organ; Parasympathetic Nervous System; Pb element; Phase; Physiopathology; Progenitor Cells; Programs (PT); Programs [Publication Type]; Pulmonary Disease, Chronic Obstructive; R01 Mechanism; R01 Program; RPG; Racial Segregation; Research; Research Grants; Research Project Grants; Research Projects; Research Projects, R-Series; Role; Screening procedure; Sensory; Sensory Cell Afferent Neuron; Signal Transduction; Signal Transduction Systems; Signaling; Smell; Smell Perception; Specific qualifier value; Specified; Stem cells; System; System, LOINC Axis 4; Taste; Taste Perception; Techniques; Technology; Testing; Training; Transgenic Organisms; Urinary System, Bladder; Vertebrate Animals; Vertebrates; Work; Zebra Danio; Zebra Fish; Zebrafish; base; biological signal transduction; cell type; disease/disorder; experiment; experimental research; experimental study; genetic mapping; genome mutation; heavy metal Pb; heavy metal lead; innervation; interest; migration; mutant; nerve supply; neuronal; novel; pathophysiology; progenitor; programs; research study; screening; screenings; segregation; sensory system; social role; tool; transgenic; urinary bladder; vertebrata
Project start date: 2007-05-01
Project end date: 2011-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2011
PFA/PA: PA-07-297
5R00HD055303-05 (2010): $246509