Cell Communication, Developmental Genetics, Epithelial Cell Biology, Fruit Fly Genetics, Cell Biology of Embryonic Development and Tissue Renewal
Ph.D. University of Colorado, Boulder
My laboratory studies how cells communicate to coordinate the formation of functioning organs. We use fruit flies as a model organism, because of the powerful genetic tools available to study cell biology in whole tissues.
In the course of a lifetime, tissues and organs must maintain their function despite environmental insults, disease, and aging. They do so using many of the same genes and proteins that were used to build the tissue during embryonic development. Both development and repair processes are tightly controlled to obtain optimal function and prevent overgrowth. In both processes, cells constantly sense their environment to make decisions about their fate, for example deciding whether to divide, migrate or differentiate. Other cells in the tissue guide these decisions by producing signals that transmit information about the state of the tissue. The resultant combination of signals coordinates individual cell decisions across the tissue to build or maintain functional architecture. Our laboratory uses the fruit fly, Drosophila melanogaster, as an experimental model to investigate the genes and proteins that cells use to detect these signals and interpret them to select the appropriate fate for tissue function. Current projects in our lab focus on two general approaches to this problem.
First, we are investigating concerted migration of epithelial cells in the fly ovary. Epithelial cells are tightly connected into an organized sheet, and are essential to the function of most organs in both flies and humans. Each fly egg is formed within a structure called a follicle, which includes both germ cells and a somatic epithelium of about 650 follicle cells. This epithelium develops together with the underlying oocyte to create a functional egg. In late oogenesis, neighboring regions of the epithelium undergo distinct migrations: either moving to cover the anterior end of the oocyte or leave the epithelium to cover the apical surface of adjacent follicle cells. To investigate the mechanisms that direct these migrations, we use are variety of techniques to examine genetically manipulated follicle cells, including time-lapse micro-imaging of cultured egg chambers. Our goal is to understand how cell-cell communication mechanisms are fine-tuned to differentiate these two neighboring cell populations and drive two distinct modes of concerted cell migrations.
Second, we are investigating the mechanisms that create a “set-point” for tissue-wide responses to a specific cell communication signal. For this approach, we are focusing on the Bone Morphogenetic Proteins (BMPs), secreted proteins that organize the growth and structure of tissues and body plans in organisms from hydra to humans. BMPs have the functional properties of developmental morphogens; when present in different concentrations they induce different cell. We are using the development of the fly wing as our experimental system, and developing computational methods to analyze image data from our experiments. Our goal is to understand how intracellular mechanisms, such as crosstalk between signal transduction pathways, constrain growth and differentiation to create a wing blade of appropriate size and structure.
- Posakony LG, Raftery LA, Gelbart WM. Wing formation in Drosophilarequires decapentaplegic gene function along the anterior-posterior compartment boundary. Mech Dev 1991; 33:69-82.
- Blackman RK, Sanicola M, Raftery LA, Gillevet T, Gelbart WM. An extensive 3' cis-regulatory region directs the imaginal disk expression of decapentaplegic, a member of the TGFbeta family in Drosophila. Development 1991; 111:657-65.
- Raftery LA, Sanicola M, Blackman RK, Gelbart WM. The relationship ofdecapentaplegic and engrailed expression in Drosophila imaginal disks: do these genes mark the anterior-posterior compartment boundary? Development 1991; 113:27-33.
- Raftery LA, Twombly V, Wharton K, Gelbart WM. Genetic screens to identify elements of the decapentaplegic signaling pathway in Drosophila. Genetics 1995; 139:241-54.
- Sekelsky JJ, Newfeld SJ, Raftery LA, Chartoff EH, Gelbart WM. Genetic characterization and cloning of Mothers against dpp, a gene required fordecapentaplegic function in Drosophila melanogaster. Genetics 1995; 139:1347-58.
- Baden H, Kollias N, Anderson RR, Hopkins T, Raftery LA. Drosophila melanogaster larvae detect low doses of UVC radiation as manifested by a writhing response. Arch Insect Biochem Physiol 1996; 32:187-96.
- Raftery LA, Wisotzkey RG. Characterization of Medea, a gene required for maximal function of the Drosophila BMP homolog, decapentaplegic. Ann. NY Acad. Sci. 1996; 785:318-320.
- Dobens LL, Hsu T, Twombly V, Gelbart WM, Raftery LA, Kafatos FC. TheDrosophila bunched gene is a homologue of the growth factor stimulated mammalian TSC22 sequence and is required for proper follicle cell patterning during oogenesis. Mech Dev 1997; 65:197-208.
- Dobens L, Raftery LA. Drosophila oogenesis: a model system to understand TGFbeta/Dpp directed cell morphogenesis. Ann NY Acad Sci 1998; 857:245-247
- Wisotzkey RG, Mehra A, Sutherland D, Dobens LL, Liu X, Dohrmann C, Attisano L, Raftery LA. Medea is a Drosophila SMAD4 homolog that is differentially required to potentiate DPP responses. Development 1998; 125:1433-144
- Brummel T, Abdollah S, Haerry TE, Shimell MJ, Merriam J, Raftery L, Wrana J, O’Connor MB. The Drosophila Activin receptor Baboon signals through dSmad2 and controls cell proliferation but not patterning during larval development. Genes Dev 1999; 13:98-111.
- Dohrmann CE, Belaoussoff M, Raftery LA. Dynamic expression of TSC-22 at sites of epithelial-mesenchymal interactions during mouse development. Mech Dev 1999; 84:147-151.
- Raftery, LA, Sutherland, DJ. From Mad to Smads: TGFb??? signal transduction in Drosophila development. Dev Biol 1999; 210:251-268.
- Dobens LL, Peterson J, Treisman J, Raftery LA. Drosophila bunchedintegrates opposing DPP and EGF signals to set the operculum boundary. Development 2000; 127:745-754.
- Dobens LL, Raftery LA. Integration of epithelial patterning and morphogenesis in Drosophila ovarian follicle cells. Dev Dyn 2000; 218:80-93.
- Dai H, Hogan C, Gopalkrishnan B, Torres-Vasquez J, Nguyen M., Park S,Raftery LA, Warrior R, Arora K. The zinc finger protein Schnurri acts as a Smad partner in mediating the transcriptional response to Dpp. Dev. Biol. 2000; 227:373-387.
- Dobens LL, Martin-Blanco E, Martinez-Arias A, Kafatos FC, Raftery LA. Drosophila puckered regulates Fos/Jun levels during follicle cell morphogenesis. Development 2001; 128:1845-1856.
- Dohrmann CE, Noramly S, Raftery LA, Morgan, B. Opposing effects on TSC-22 expression by BMP and receptor tyrosine kinase signals in the developing feather field. Dev. Dyn. 2002; 223:85-95.
- Gupta RA, Sarraf P, Brockman JA, Shappell SB, Willson TM, Raftery, L, DuBois, RN. Peroxisome proliferator-activated receptor g and transforming growth factor-b pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22. J Biol Chem 2003; 278:7431-7438
- Soma T, Dohrmann CE, Hibino T, Raftery LA. Profile of TGFbeta responses in the murine hair cycle. J Inv Derm: 2003; 121:969-975.
- Sutherland DJ, Li M, Liu X, Stefancsik R, Raftery LA. Stepwise formation of a Smad activity gradient during dorsal-ventral patterning of the Drosophila embryo. Development 2003; 130:5705- 5716.
- Raftery, LA, Sutherland, DJ Gradients and Thresholds: BMP response gradients unveiled in Drosophila embryos. Trends Genet 2003; 19:667-724.
- Whitman M, Raftery L TGRbeta at the summit. Development 2005; 132(19): 4205-4210.
- Dobens L, Jaeger A, Peterson JS, Raftery LA bunched sets a boundary for Notch signaling to pattern anterior eggshell structures during Drosophilaoogenesis. Dev. Biol. 2005: 287:425-437.
- Raftery LA, Korochkina S, Cao J. “Smads in Drosophila – interpretation of graded signals in vivo.” in Smad Signal Transduction, C-H Heldin, P ten Dijke, eds. Springer, 2006, 55-73.
- Cao J, Pellock BJ, White K, Raftery LA. A commercial phospho-Smad antibody detects endogenous BMP signaling in Drosophila tissues. Drosophila Information Service 2006: 89:131-135
- Gluderer S, Köhler K, Oldham S, Rintelen F, Sulzer A, Schütt C, Wu X, Raftery L, Hafen E, Stocker H. Bunched, the Drosophila homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth. BMC Dev. Biol. 2008 8:10.
- Wu X, Tanwar PS, Raftery LA, Drosophila follicle cells: morphogenesis in an eggshell. Seminars Cell Dev. Biol. 2008; 19:271-282.
- Wu X, Yamada-Mabuchi M, Morris EJ, Gluderer S, Tanwar P, Dobens L, Cao J, Stocker H, Hafen E, Dyson NJ, Raftery LA. The Drosophila homolog of human tumor suppressor TSC-22 promotes cellular growth, proliferation and survival. Proc. Natl. Acad. Sci. 2008; 105:5414-5419.
- Bilenca A, Cao J, Colice M, Ozcan A, Bouma B, Raftery L, Tearney G. Fluorescence interferometry: principles and applications in biology. Ann. N.Y. Acad. Sci. 2008; 1130:68-77.
- Batut J, Schmierer B, Howell M, Cao J, Raftery LA, Hill CS. Two highly related regulatory subunits of PP2A exert opposite effects on TGFbeta signaling. Development 2008: 135:2927-2937
- Miles WO, Jaffray E, Campbell SG, Takeda S, Bayston LJ, Basu SP, Li M, Raftery LA, Ashe MP, Hay RT, Ashe HL. Medea SUMOylation restricts the signaling range of the Dpp morphogen in the Drosophila embryo. Genes Dev. 2008; 22:2578-2590.
- Raftery LA, Umulis, D Generation and interpretation of BMP gradients in Drosophila, Cur. Opin. Cell Biol. 2012, 24:1-8
- Brooks AI, Dou W, Pargett M, Brosnan T, Raftery LA, Umulis DM. BMP signaling in development: A critical analysis of imaging and interpretation. FEBS Lett. 2012, 586:1942-1952
- Peterson AJ, Jensen PA, Shimell MJ, Stefancsik R, Wijayatunge R, Herder R, Raftery LA, O'Connor MB.. R-Smad competition controls Activin receptor output in Drosophila. PLoS One 2013, 7: e36548
SEB Program Group: Integrative Physiology
SEB Lab Location: 3155/3156
SEB Lab Phone Number: 702-774-1474