Waksman Institute of Microbiology, School of Arts and Sciences, New Brunswick; Waksman Institute of Microbiology, Centers, Institutes, Other; Rutgers
Areas of Interest
Oogenesis, Pattern Formation and Immune Response in Drosophila.
Academic Interests and Plans
Our work on dorsal concentrates on two major questions. How is the dorsal nuclear protein gradient established, and how does dorsal protein function once it is in the nucleus? We are studying the importance of phosphorylation of dorsal protein for its function, and we are using biochemical and genetic approaches to isolate new genes that function in the establishment of the dorsal nuclear gradient.
The dorsal gene of a Drosophila encodes the last step in the maternal signal transduction pathway that results in dorsal-ventral polarity. Dorsal is the ventral morphogen that instructs ventral and lateral cells as to their identity, and is a member of the Rel family of transcription factors that also includes the lymphocyte transcription factor NF-kB, the viral oncogene v-rel, and v-rel's cellular homolog, c-rel. The activity of dorsal is regulated posttranslationally. It is found in an inactive form in the cytoplasm of early embryos and is present in a ventral-to-dorsal nuclear gradient in blastoderm stage embryos. Once in the nucleus, dorsal protein acts as a transcriptional activator as well as a repressor of different zygotic genes within the same nucleus.
Genetic studies show that the maternal Bicaudal-D gene product is involved in localizing determinants at the posterior end of the early embryo and that it is also essential for the differentiation of the oocyte early in oogenesis, most likely by localizing oocyte determinants as RNAs in the prospective oocyte. We have shown that both the Bicaudal-D RNA and protein accumulate in the prospective oocyte and that the localization of the Bicaudal-D and other RNAs in the oocyte is dependent on the accumulation of Bicaudal-D protein.
The Bicaudal-D protein shows similarity to myosin heavy chain tails, paramyosin, and kinesin, and so may be involved in transporting RNAs to specific domains of the oocyte. We are investigating these possibilities by identifying proteins associated with Bicaudal-D genetically and biochemically. We are also determining the function of the localization of the RNA and protein and studying which sequences are necessary for the localization.
A third project focuses on nuclear migration. We have cloned the Drosophila homolog of the human Lis-1 gene, that is affected in children with Lisencephaly, a strong disorder in brain development. In Aspergillus the Lis-1 homolog, NudF, has been isolated as a mutation in which nuclear migration is abolished. We plan to use Drosophila genetics to investigate different aspects of nuclear migration and its possible involvement in cell migration.