Wednesday, May 21, 2025
5/21/2025
ACTIVITY OF DPAX2 IN GLIAL CELL DIFFERENTATION - DESCRIPTION (provided by applicant): The ability of developing organisms to allocate appropriate differentiative fates to cells within a given lineage is of paramount importance. When the mechanisms that govern such events fail, disease states occur. Such diseases in humans can be congenital or acquired. In addition, it has become evident that a solid understanding of the processes that determine cell fate will be essential to the new wave of medical technologies, such as treatment of diseases via stem cell transplants and the in vitro generation of tissues and organs. To this end, we propose to investigate the mechanisms that determine a glial vs. neuron cell fate decision using the development of the Drosophila mechanosensory organ as a model. This decision is controlled by the Notch signaling pathway and results in the specific expression of the transcription factor dPax2 in the glial cell but not the neuron. Notch signaling is central to a multitude of developmental processes in humans and is involved in cancers such as certain T cell leukemias. The human homolog of dPax2 is defective in renal coloboma syndrome and has been associated with Wilms tumor. We will examine the control of dPax2, expression by Notch signaling and the role of dPax2 in glial cell differentiation as follows: 1. Notch signaling will be manipulated during Drosophila development with the use of existing mutants and the effect on dPax2 expression in sense organ lineage cells will be examined. 2. The transcriptional regulation of the dPax2 gene will be investigated by (a) sequence analysis of the 5' regulatory region of dPax2 in wild-type and dPax2 mutant flies and (b) generation of transgenic fly lines bearing fragments of the 5' dPax2 regulatory region adjacent to the reporter gene GAL4. 3. Using the GAL4-UAS system, the dPax2 gene will be misexpressed in neurons and other cell types during development. The effects of such treatment on cell fate and differentiation will be examined.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).