[' ', ' ', ' ', '0150274', 'IDENTIFYING', 'NO.:', '5RO1NS13079-19', 'AGENCY', 'CODE:', 'CRISP', 'HORMONE', 'ACTION', 'ON', 'THE', 'CENTRAL', 'NERVOUS', 'SYSTEM', 'PRINCIPAL', 'INVESTIGATOR:', 'TRUMAN,', 'JAMES', 'W', 'ADDRESS:', 'UNIVERSITY', 'OF', 'WASHINGTON', 'SEATTLE,', 'WA', '98195', 'PERFORMING', 'ORG.:', 'UNIVERSITY', 'OF', 'WASHINGTON,', 'SEATTLE,', 'WASHINGTON', 'SPONSORING', 'ORG.:', 'NATIONAL', 'INST', 'OF', 'NEUROLOGICAL', 'DISORDERS', 'AND', 'STROKE', 'FY', ':', 'G4', 'FUNDS:', '$248,428', 'TYPE', 'OF', 'AWARD:', 'Noncompeting', 'Continuation', '(Type', '5)', 'SUMMARY:', 'The', 'tobacco', 'hornworm,', 'Manduca', 'sexta,', 'and', 'the', 'fruit', 'fly,', 'Drosophila,', 'are', 'favorable', 'experimental', 'material', 'in', 'which', 'to', 'examine', 'the', 'developmental', 'effects', 'of', 'hormones', 'on', 'the', 'CNS.', 'During', 'larval', 'life,', 'both', 'species', 'show', 'extensive', 'neurogenesis', 'which', 'can', 'be', 'quantified', 'by', 'incorporation', 'of', 'bromodeoxyuridine', 'into', 'the', 'DNA', 'of', 'dividing', 'cells', 'followed', 'by', 'immnocytochemistry.', 'With', 'this', 'tool,', 'the', 'extrinsic', 'factors', 'regulating', 'neurogenesis', 'in', 'noxmal', 'larvae', 'can', 'be', 'determined.', 'Cell', 'proliferation', 'mutants', 'in', 'Drosophila', 'will', 'then', 'be', 'screened', 'for', 'those', 'which', 'interfere', 'with', 'various', 'aspects', 'of', 'neurogenesis.', 'Culturing', 'of', 'neuroblasts', 'from', 'mutant', 'and', 'wild-type', 'animals', 'will', 'further', 'clarify', 'the', 'role', 'of', 'intrinsic', 'and', 'extrinsic', 'factors', 'in', 'regulating', 'neurogenesis.', 'The', 'mechanisms', 'by', 'which', 'hormones', 'bring', 'about', 'the', 'programmed', 'death', 'of', 'mature', 'neurons', 'will', 'be', 'examined.', 'Drosophila', 'will', 'be', 'screened', 'for', 'mutants', 'that', 'interfere', 'with', 'this', 'programmed', 'death.', 'Also,', 'labeled', 'steroids', 'and', 'autoradiography', 'will', 'be', 'used', 'in', 'the', 'moth', 'to', 'further', 'define', 'the', 'relationship', 'of', 'hormone', 'target', 'cells', 'to', 'cells', 'that', 'die.', 'During', 'larval', 'life,', 'the', 'insect', 'CNS', 'produces', 'discrete', 'nests', 'of', 'cells,', 'each', 'arising', 'from', 'a', 'single,', 'identifiable', 'neuroblast.', 'After', 'their', 'birth', 'the', 'cells', 'arrest', 'at', 'a', 'point', 'before', 'extensive', 'process', 'outgrowth', 'and', 'transmitter', 'expression.', 'Later,', 'these', 'cells', 'then', 'mature', 'into', 'functional', 'neurons', 'during', 'metamorphosis', 'in', 'response', 'to', 'circulating', 'ecdysteroids.', 'A', 'series', 'of', 'in', 'vivo', 'and', 'in', 'vitro', 'experiments', 'will', 'examine', 'the', 'regulation', 'of', 'differentiation', 'of', 'thease', 'cella', 'in', 'response', 'to', 'the', 'steroid', 'signal.', 'Neurons', 'produced', 'by', 'specific', 'lineages', 'will', 'be', 'defined', 'by', 'antibodies', 'against', 'various', 'transmittera.', 'Using', 'chemical', 'ablation', 'techniques,', 'neuroblasts', 'will', 'be', 'killed', 'at', 'various', 'times', 'to', 'allow', 'examination', 'of', 'the', 'relationship', 'of', 'lineage', 'size', 'to', 'the', 'subsequent', 'differentiation', 'of', 'its', 'members.', 'Specific', 'lineage', 'groups', 'will', 'be', 'cultured', 'and', 'their', 'differentiation', 'in', 'vitro', 'in', 'response', 'to', 'steroida', 'will', 'be', 'compared', 'to', 'their', 'normal', 'fate', 'in', 'vivo.', '6/7/56', 'DIALOG', '(R)File', '266:Fed.', 'Res.', 'in', 'Progress', '{c)', 'format', 'only', '1995', 'Dialog', 'Info.Svcs.', 'All', 'rta,', 'reserv.', '0150203', 'IDENTIFYING', 'NO.:', '5R0iNS11549-21', 'AGENCY', 'CODE:', 'CRISP', 'SYNAPSE', 'FORMATION', 'AND', 'NEOROMUSCULAR', 'DISEASE', 'PRINCIPAL', 'INVESTIGATOR:', 'HEINEMANN,', 'STEPHEN', 'F', 'ADDRESS:', 'SALK', 'INST', 'FOR', 'BIOLOGICAL', 'STUDI', 'PO', 'BOX', '85800', 'SAN', 'DIEGO,', 'CA', '92186-5800', 'PERFORMING', 'ORG.:', 'SALK', 'INSTITUTE', 'FOR', 'BIOLOGICAL', 'STUDIES,', 'SAN', 'DIEGO,', 'CALIFORNIA', 'SPONSORING', 'ORG.:', 'NATIONAL', 'INST', 'OF', 'NEUROLOGICAL', 'DISORDERS', 'AND', 'STROKE', 'FY', 'i', '94', 'FUNDS:', '$525,092', 'TYPE', 'OF', 'AWARD:', 'Noncompeting', 'Continuation', '(Type', '5)', '.', 'SUMMARY:', 'The', 'goal', 'of', 'this', 'research', 'is', 'to', 'understand', 'the', 'physiological', 'xole', 'of', 'the', 'family', 'of', 'nicotinic', 'acetylcholine', 'receptor', 'genes', 'that', 'has', 'been', 'discovered', 'in', 'the', 'mammalian', 'genome.', 'One', 'set', 'of', 'genes', 'codes', 'for', 'the', 'nicotinic', 'acetylcholine', 'receptors', 'that', 'are', 'present', 'at', 'the', 'neuromuscular', 'junction', 'in', 'skeletal', 'muscle,', 'This', 'receptor', 'is', 'the', 'target', 'of', 'the', 'autoimmune', 'response', 'in', 'the', 'disease', 'myasthenia', 'gravis.', 'Recombinant', 'DNA', 'techniques', 'will', 'ba', 'used', 'to', 'locate', 'the', 'region', 'of', 'the', 'receptor', 'that', 'is', 'the', 'main', 'site', 'of', 'attack', 'by', 'the', 'immune', 'system.', 'The', 'relationship', 'between', 'the', 'structure', 'of', 'the', 'acetylcholine', 'receptor', 'and', 'the', 'function', 'of', 'the', 'receptor', 'will', 'be', 'elucidated', 'by', 'means', 'of', 'site', 'specific', 'mitagenesis,', 'The', 'promoter', 'regions', 'of', 'the', 'receptor', 'will', 'be', 'studied', 'in', 'order', 'to', 'understand', 'how', 'electrical', 'activity', 'regulates', 'fest', 'SESZ', 'OPTTS', ' ']