[ Research Interests ] [ Representative Publications ]

Allan C. Spradling, Ph.D. Adjunct Professor Department of Biology Director Department of Embryology, Carnegie Institution of Washington B.A. University of Chicago Ph.D. Massachusetts Institute of Technology

Carnegie Institution of Washington 3520 San Martin Drive Baltimore, MD 21218 U.S.A. Office Lab Fax: Email: 410.246.3013 410.246.3038 410.243.6311 spradling@ciwemb.edu Carnegie Institution of Washington

Research Interests My laboratory studies the biology of reproduction. Eggs are remarkable cells, that by unknown means reset the normally irreversible processes of differentiation and aging that govern all somatic cells. We use Drosophila as our primary research system, because these processes are likely to be conserved in all metazoan organisms and Drosophila currently provides the experimentally most favorable multicellular system for molecular genetic studies. We focus on several aspects of oogenesis that promise to provide insight into nuclear and cytoplasmic rejuvenation. By studying ovarian stem cells, we are learning how cells maintain an undifferentiated state and how cell production is regulated by microenvironments known as niches. We have found that epithelial stem cells responsible for follicle cell production compete. Replacement of damaged stem cells may be a major mechanism that limits somatic mutation, but we hae also found that mutations exist that confer the ability to replace wild type cells. Such mutations may be precursors to cellular aging and cancer. We also believe that an elaborate system of organelle sorting during the time germ cells are interconnected prior to meiosis contributes to the removal of damaged mitochondrial DNA molecules, and possibly also acts on damaged proteins. Finally, in order to understand better how these complex processes are controlled, we are re-investigating the role of steroid and prostaglandin hormones in controlling the process of oogenesis, from stem cell to laid egg. Representative Publications Tootle, T. and Spradling, A.C. 2008. Drosophila Pxt: a cyclooxygenase-like facilitator of follicle maturation. Development. (In press). Allen, A. and Spradling, A.C. 2008.  The SF-1-like nuclear hormone receptor Hr39 regulates Drosophila female reproductive tract development and function.  Development. 135:311-321. Nystul, T. and Spradling, A.C. 2007. An epithelial niche in the Drosophila ovary undergoes long range stem cell replacement. Cell Stem Cell 1, 277-285. Fuller, M. and Spradling, A.C. 2007. The male and female Drosophila germline stem cell niches: two versions of immortality. Science 316, 402-404. Spradling AC, Zheng Y. 2007. The mother of all stem cells? Science 315: 469-70. Ohlstein, B. and A.C. Spradling 2007. Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential Notch signaling. Science 315, 988-92. Cox, R. and Spradling, A.C. 2006. Milton controls the initial acquisition of mitochondria by Drosophila oocytes. Development 133, 3371-7. Ohlstein, B and A.C. Spradling 2006. The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 439, 470-474. Epub Dec 7, 2005 deCotto, E. and Spradling, A.C. 2005. The male and female Drosophila germline stem cell niche: similar cells and signals. Devel. Cell 9, 501-510. Kai, T. and A.C. Spradling 2004. Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries. Nature 428, 564-9. Tulin, A., Stewart, D. and Spradling, A.C. 2002.  The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP) is required to modulate chromatin structure during development. Genes and Develop. 16, pp 2108-2119. Spradling, A.C., Drummond-Barbosa, D. and Kai, T. 2001.  Stem cells find their niche. Nature 414, pp 14-18. Pepling, M. and Spradling, A.C. 2001.  The mouse ovary contains germ cell cysts that undergo programmed breakdown to form follicles. Dev. Biol. 234, pp 339-351. Fyrdman, H. and Spradling, A.C. 2001. The receptor-like tyrosine phosphatase LAR is required for epithelial planar polarity and for axis determination within Drosophila ovarian follicles. Development 128, pp 3209-3220. Xie, T. and Spradling, A.C. 2000. A stem cell niche maintaining germ cell production in the Drosophila ovary. Science 290, pp 328-330. Dej, K. and Spradling, A.C. 1999.  The endocycle controls nurse cell polytene chromosome structure during Drosophila oogenesis. Development 126, pp 293-303.

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