Stem Cells & Spermatogenesis
 
Cells within certain lineages are continually replenished throughout the life of the organism. This is accomplished by the activity of stem cells. Such cells divide asymmetrically, generating one cell that retains self-renewing stem cell capacity, and a second daughter cell that "transiently amplifies" the cell pool by executing a limited number of mitoses before differentiating into a specialized cell type. Regulation of stem cell behavior is crucial for the renewal of tissues such as blood, skin, nervous system, intestine and male germ line. Regulation of the transient amplifying cells assures proper expansion of the differentiated cell types. In addition, recent discoveries highlight an unexpected significance of transient amplifying cells, since these cells can "de-differentiate" into new stem cells. We focus our research on the fundamental property common to all tissues maintained by a stem cell population – the need to balance self-renewal with differentiation. Mechanisms governing these behaviors are poorly understood. We investigate Drosophila spermatogenesis as a model stem cell system. We have identified mutations that affect self-renewal, differentiation and transit amplification, and are using these mutants in combination with experimental and genomic approaches, such as microarray analysis and GFP-protein exon trapping, to investigate the mechanisms involved. Given the conservation of developmental mechanisms among species, we are now also extending our analysis to mouse spermatogonial stem cells, to test directly the prospect that our results in the fly will apply to other stem cell lineages. Representative Publications on Stem Cell Function 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, in press N. Terry, N. Tulina, E. Matunis and S. DiNardo. (2006) "Novel intrinsic and extrinsic regulators revealed by profiling Drosophila testis stem cells within their niche". Developmental Biology 294, 246 – 257. Wallenfang, M., Nayak, R. and DiNardo, S. (2006) “Dynamics of the male germline stem cell population during aging of Drosophila melanogaster”.Aging Cell 5, 297-304 (with cover).