William Tan

Graduate Student

  • p: (848) 445-3918

Research Summary
Fragile-X Syndrome is most commonly inherited form of cognitive impairment, and the disease can result in a variety of symptoms including autism, infertility and other developmental disorders. Fragile-X Syndrome is caused by a reduction in the levels of Fragile-X Mental Retardation Protein (FMRP). FMRP functions by selectively binding mRNA targets in the nucleus and subsequently inhibiting initiation of translation at the ribosome. ). Drosophila melanogaster (fruit fly) is a well-characterized model system for studying FMRP and its targets. In Drosophila FMRP has been shown be required for a number of developmental processes, including maintenance of both neural and ovary germline stem cells.

Zfrp8 is another stem cell maintenance protein essential in a number of different Drosophila stem cell populations, including hematopoietic stem cells, ovarian stem cells and intestinal stem cells. In mouse models, Zfrp8 is required to maintain cell viability and proliferation during early embryogenesis. We have identified Zfrp8 as a novel component of the FMRP complex. Immunoprecipitation results show that Zfrp8 physically interacts in a protein complex containing FMRP, the Ribosomal Protein S2 homolog, and Nufip (Nuclear Fragile-X Mental Retardation Interacting Protein). In order to determine the relationship between Zfrp8 and FMRP, I have analyzed FMRP activity and protein levels in Zfrp8 mutants. Western blot analysis of Zfrp8 mutant larva show an overall increase in FMRP levels during the Drosophila larval stages. In addition, FMRP target Me31B is mislocalized in Zfrp8 mutants. These results point to a novel regulatory role for the Zfrp8 protein in the FMRP pathway. Studying the Zfrp8-FMRP interaction gives us a new insight into the processes that control stem cell maintenance and proliferation.