Research Interests:
Cells within tissues and organs are continually replenished throughout life. This is accomplished by special “stem cells”. These cells are responsible for intestinal, skin, muscle and blood cell function. Therapies based on the manipulation of stem cells have the potential to revolutionize medicine. The excitement is due to the fundamental property of stem cells: these cells balance self-renewal with the production of the more differentiated cell types necessary for tissue function. The mechanisms that control this balance are unclear. Thus, there is a need to investigate stem cell-based tissues where molecular genetic and genomic approaches may be used.

In initiating spermatogenesis, stem cells of the male germline choose between self-renewal and lineage progression. The DiNardo lab pioneered the use of Drosophila spermatogenesis as a model stem cell system, and we are now collaborating with the Brinster lab, which focuses on mammalian (mouse) germline spermatogonial stem cell (GSC) function. Spermatogenesis is quite similar comparing mouse and fruitfly, with both maintained by GSC populations and special somatic cells that comprise the stem cell’s “niche”. Yet no systematic effort has been made to explore whether there exist any common mechanisms that control GSC function. The strengths of each species are complementary: for mouse, a transplantation assay for GSC’s, including viral infection and gene delivery, and a significant purification of a functional GSC population; for fly, knowledge of the in situ localization of GSC’s, as well as relevant niche cells, and analysis of their behavior and regulation by genetic approaches that afford single-cell resolution. For these reasons we are testing collaboratively and at a genomics level the hypothesis that there exist conserved mechanisms governing the behavior of GSC’s in these two species.


Rotation Projects on Stem Cell Behavior during Spermatogenesis:
Students will participate in the identification of both extrinsic signal and intrinsically–acting factors that regulate progression through the germline stem cell lineage. Projects include functional tests of genes we identified as niche-enriched by expression profiling, using state-of-the-art high-resolution techniques in Drosophila, and the exploration of “winners” in mouse GSC biology.

Recent Representative Publications:
Fabrizio, J. J., Boyle, M., and DiNardo, S. (2003). A somatic role for eyes absent (eya) and sine oculis (so) in Drosophila spermatocyte development. Dev Biol 258, 117-28.

Kauffman, T., Tran, J., and DiNardo, S. (2003). Mutations in Nop60B, the Drosophila homolog of human dyskeratosis congenita 1, affect the maintenance of the germ-line stem cell lineage during spermatogenesis. Dev Biol 253, 189-99.

Tolwinski, N. S., Wehrli, M., Rives, A., Erdeniz, N., DiNardo, S., and Wieschaus, E. (2003). Wg/Wnt signal can be transmitted through arrow/LRP5,6 and Axin independently of Zw3/Gsk3beta activity. Dev Cell 4, 407-18.

Hatini, V., Green, R. B., Lengyel, J. A., Bray, S. J., and Dinardo, S. (2005). The Drumstick/Lines/Bowl regulatory pathway links antagonistic Hedgehog and Wingless signaling inputs to epidermal cell differentiation. Genes Dev 19, 709-18.

Walters, J. W., Munoz, C., Paaby, A. B., and Dinardo, S. (2005). Serrate-Notch signaling defines the scope of the initial denticle field by modulating EGFR activation. Dev Biol 286, 415-26.Rives, A. F., Rochlin, K. M., Wehrli, M., Schwartz, S. L., and DiNardo, S. (2006). Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing. Dev Biol 293, 268-83.

Terry, N. A., Tulina, N., Matunis, E., and DiNardo, S. (2006). Novel regulators revealed by profiling Drosophila testis stem cells within their niche. Dev Biol 294, 246-57.

Wallenfang, M. R., Nayak, R., and DiNardo, S. (2006). Dynamics of the male germline stem cell population during aging of Drosophila melanogaster. Aging Cell 5, 297-304.

Walters, J. W., Dilks, S. A., and DiNardo, S. (2006). Planar polarization of the denticle field in the Drosophila embryo: roles for Myosin II (zipper) and fringe. Dev Biol 297, 323-39.

Franklin-Dumont, T. M., Chatterjee, C., Wasserman, S. A., and Dinardo, S. (2007). A novel eIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation in Drosophila spermatocytes. Development 134, 2851-2861 doi:10.1242/dev.003517: highlighted with an, “In this issue”, using our figure.