Discipline: Biological Sciences
Esmeralda Montes - University of California, Los Angeles
Co-Author(s): Gabriel Ferguson and Julian A. Martinez-Agosto, University of California, Los Angeles, CA
Children are often born or can develop PTEN Hamartoma Tumor Syndromes (PHTS) and Tuberous Sclerosis Complex (TSC), causing an increase in brain tissue growth, ramifying into intellectual disabilities, autism spectrum disorders or seizures. PHTS and TSC are rare genetic syndromes characterized by mutations of the tumor suppressor genes phosphatase and tensin homolog (PTEN) and TSC, which are driven by cellular overgrowth leading to hamartomas in virtually any organ. TSC and PTEN are negative regulators of phosphatidylinositol 3kinase (PI3K) pathway resulting in regulation of downstream targets responsible for tissue growth during development. The objective of this study was to assess if there was an increase in cell growth within wing imaginal disc of Drosophila by downregulating PTEN and TSC, and if starvation of offsprings would return disc back to normal size. Apterous green fluorescent protein (ApGFP) flies, expressing GFP when ApGal4 is present, result in green fluorescence on the dorsal side of the wing, were crossed with flies containing RNA interference (RNAi) constructs, which would inhibit gene expression. Using confocal microscopy to analyze the effects of RNAi, larvae first underwent specific antibody staining: TO-PRO to locate the nucleus, phH3 to identify the cells undergoing mitosis, and p4EBP to illustrate the activation of the P13K pathway. We then obtained more offsprings from the crosses and placed them in starvation plates. Both PTEN and TSC expressed an increase within wing imaginal disc when stained. As a result, we can better understand how tissue growth functions when tumor suppressors are altered, and how they regulate a final organ tissue. Through this we would like to better comprehend human genetic conditions; such as PHTS and TSC. As a result, we are hopeful that in the near future we can aid in developing a novel way of treating these conditions.
Funder Acknowledgement(s): I would like to thank my faculty mentor, Dr. Martinez, direct mentor Dr. Ferguson, as well as every member of the lab for supporting and influencing my growth as a researcher. This study was supported, by a grant from the NIH awarded to Dr. Simmons, director of the Minority Access to Research Careers (MARC) program at University of California, Los Angeles, CA.
Faculty Advisor: Julian A. Martinez-Agosto,