The ability to functionally test the effects of specific DNA sequences on developmental regulation (e.g. transcription and RNA processing) by gene transfer and analysis of modified genes in vivo provides a new dimension to the study of developmental regulation in metazoans. While the foundation of our understanding of genetic regulation comes from studies on prokaryotes and lower eukaryotes (e.g. fungi), the vast majority of these studies have examined the regulation of catalytic gene products (i.e. enzymes) in a variety of highly regulated metabolic pathways while genes studied in metazoans have been largely noncatalytic structural genes. The dopa decarboxylase (Ddc) and lambda (2)amd genes of Drosophila catechol metabolism are an ideal set of catalytic gene products in a single metabolic pathway that are amenable to genetic, developmental, and molecular analysis. Four specific questions are posed which will help us understand some general properties of developmental regulation. Is the expression of these metabolically related genes coordinated and, if so, how? What is the location and nature of the contiguous DNA encoded signals which govern control of developmental expression of these genes? What is the developmental significance of differential RNA processing in these genes? How are these genes organized in the genome and what is the functional or evolutionary significance of the organization? We have used transposon mediated gene transfer of cloned Ddc and amd DNA to rescue mutant embryos. In this study we will construct a series of gene fusions and specific alterations which can be functionally tested in vivo by transposon mediated transformation. These experiments will provide direct evidence for specific localization of regulatory signals controlling developmental expression of these catechol metabolizing enzymes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028972-08
Application #
3276388
Study Section
Genetics Study Section (GEN)
Project Start
1981-04-01
Project End
1991-01-31
Budget Start
1989-08-01
Budget End
1991-01-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Konrad, K D; Goralski, T J; Mahowald, A P et al. (1998) The gastrulation defective gene of Drosophila melanogaster is a member of the serine protease superfamily. Proc Natl Acad Sci U S A 95:6819-24
Chang, Y T; Hyland, K; Mues, G et al. (1997) Human hair follicles as a peripheral source of tyrosine hydroxylase and aromatic L-amino acid decarboxylase mRNA. Neurosci Lett 222:210-2
Wang, D; Marsh, J L; Ayala, F J (1996) Evolutionary changes in the expression pattern of a developmentally essential gene in three Drosophila species. Proc Natl Acad Sci U S A 93:7103-7
Wang, D; Marsh, J L (1995) Developmental regulation of the alpha-methyldopa hypersensitive gene of Drosophila melanogaster. Dev Biol 168:598-612
Mason, E D; Konrad, K D; Webb, C D et al. (1994) Dorsal midline fate in Drosophila embryos requires twisted gastrulation, a gene encoding a secreted protein related to human connective tissue growth factor. Genes Dev 8:1489-501
Theisen, H; Purcell, J; Bennett, M et al. (1994) dishevelled is required during wingless signaling to establish both cell polarity and cell identity. Development 120:347-60
Wang, Z; Crowe, R R; Marsh, J L (1993) An SspI polymorphism for the human DOPA decarboxylase (DDC) gene on chromosome 7p. Hum Mol Genet 2:2198
Konrad, K D; Wang, D; Marsh, J L (1993) Vitelline membrane biogenesis in Drosophila requires the activity of the alpha-methyl dopa hypersensitive gene (I(2)amd) in both the germline and follicle cells. Insect Mol Biol 1:179-87
Scherer, L J; McPherson, J D; Wasmuth, J J et al. (1992) Human dopa decarboxylase: localization to human chromosome 7p11 and characterization of hepatic cDNAs. Genomics 13:469-71
Eveleth, D D; Marsh, J L (1987) Overlapping transcription units in Drosophila: sequence and structure of the Cs gene. Mol Gen Genet 209:290-8

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