COUREY LAB RESEARCH

	Drosophila and human development are homologous processes. They utilize closely related genes working in highly conserved regulatory networks. Unlike humans, Drosophila is subject to easy genetic manipulation. As a result, most of what we know about the molecular basis of animal development has come from studies of model systems such as Drosophila.

OVERVIEW - THE MOLECULAR BASIS OF DEVELOPMENT

During embryogenesis, a cluster of apparently undifferentiated cells is transformed into an ordered array of differentiated tissues. Using Drosophila as a model system, my research group combines biochemical and genetic approaches to study the molecular basis of this amazing transformation. Essentially all the regulatory circuits we study are conserved throughout the animal kingdom. Therefore, our studies have important implications for human health and development.

The following two major projects are currently underway in the lab.

·        Spatial and temporal regulation of transcription in development. We have been extensively examining mechanisms of activation and repression by the Dorsal morphogen, a transcription factor that determines the dorsal/ventral axis during early development. This factor is the Drosophila homolog of the vertebrate regulatory protein NF-kB. Like Dorsal, NF-kB is involved in both the determination of embryonic polarity and in the innate immune response. Furthermore, both Dorsal and NF-kB are regulated by homologous signal transduction cascades that control transcription factor activity by regulating nuclear import. [More information]

·        Role of Sumo-conjugation in development. Sumo is a recently discovered member of the ubiquitin family that is conserved throughout all eukaryotes. This polypeptide is a substrate for a protein conjugation system, in which Sumo becomes covalently attached to numerous target proteins modifying their behavior in various ways. We are attempting to learn about the roles of Sumo in cell biology and development. Our analysis has revealed possible roles for this process in regulated nuclear import, embryonic pattern formation, the immune response, and the stress response. [More information]

 

Pan, D.J., J.D. Huang, and A.J. Courey. Functional Analysis of the Drosophila twist Promoter Reveals a Dorsal-Binding Ventral Activator Region.  Genes Dev.  5, 1892-1901 (1991).

Pan, D. and A.J. Courey. The same dorsal binding site mediates both activation and repression in a context-dependent manner.  EMBO J.  11, 1837-42 (1992).

Huang, J., D.H. Schwyter, J.M. Shirokawa, and A.J. Courey. The Interplay Between Multiple Enhancer and Silencer Elements Defines the Pattern of Decapentaplegic Expression.  Genes Dev.  7, 694-704 (1993).

Pan, D., S.A. Valentine, and A.J. Courey. The bipartite D. melanogaster twist promoter is reorganized in D. virilis.  Mech. Dev.  46, 41-53 (1994).

Courey, A.J. and J.D. Huang. The establishment and interpretation of transcription factor gradients in the Drosophila embryo.  Biochim. Biophys. Acta  1261, 1-18 (1995).

Huang, J.D., T. Dubnicoff, G.J. Liaw, Y. Bai, S.A. Valentine, J.M. Shirokawa, J.A. Lengyel, and A.J. Courey. Binding sites for transcription factor NTF-1/Elf-1 contribute to the ventral repression of decapentaplegic.  Genes Dev.  9, 3177-89 (1995).

Dubnicoff, T., S.A. Valentine, G. Chen, T. Shi, J.A. Lengyel, Z. Paroush, and A.J. Courey. Conversion of dorsal from an activator to a repressor by the global corepressor Groucho.  Genes Dev.  11, 2952-7 (1997).

Shirokawa, J.M. and A.J. Courey. A direct contact between the dorsal rel homology domain and Twist may mediate transcriptional synergy.  Mol. Cell. Biol.  17, 3345-55 (1997).

Chen, G., P.H. Nguyen, and A.J. Courey. A role for Groucho tetramerization in transcriptional repression.  Mol. Cell. Biol.  18, 7259-68 (1998).

Valentine, S.A., G. Chen, T. Shandala, J. Fernandez, S. Mische, R. Saint, and A.J. Courey. Dorsal-mediated repression requires the formation of a multiprotein repression complex at the ventral silencer.  Mol. Cell. Biol.  18, 6571-6583 (1998).

Chen, G., J. Fernandez, S. Mische, and A.J. Courey. A functional interaction between the histone deacetylase Rpd3 and the co-repressor Groucho in Drosophila development.  Genes Dev.  13, 2218-2230 (1999).

Bhaskar, V., S.A. Valentine, and A.J. Courey. A functional interaction between dorsal and components of the smt3 conjugation machinery.  J Biol Chem  275, 4033-40 (2000).

Flores-Saaib, R.D. and A.J. Courey. Regulation of dorso/ventral patterning in the Drosophila embryo by multiple dorsal-interacting proteins.  Cell Biochem Biophys  33, 1-17 (2000).

Flores-Saaib, R.D. and A.J. Courey. Analysis of Groucho-histone interactions suggests mechanistic similarities between Groucho- and Tup1-mediated repression.  Nucleic Acids Res  28, 4189-96. (2000).

Courey, A.J. and S. Jia. Transcriptional repression: the long and the short of it.  Genes Dev.  15, 2786-96. (2001).

Flores-Saaib, R.D., S. Jia, and A.J. Courey. Activation and repression by the C-terminal domain of Dorsal.  Development  128, 1869-79. (2001).

Bhaskar, V., M. Smith, and A.J. Courey. Conjugation of Smt3 to Dorsal may potentiate the Drosophila immune response.  Mol. Cell. Biol.  22, 492-504 (2002).

Jia, S., R.D. Flores-Saaib, and A.J. Courey. The Dorsal Rel homology domain plays an active role in transcriptional regulation.  Mol. Cell. Biol.  22, 5089-99. (2002).