Dr. Fani Papagiannouli
Dr. Fani Papagiannouli
Im Neuenheimer Feld 230
Fon +49 6221 54-5519
Fax +49 6221 54-6424
fani.papagiannouli AET cos.uni-heidelberg.de
Stem cells are indispensable for multicellular development since they provide the cells that built up our bodies and renew damaged cells during adult life. Specialized inputs for their proper function lay in a local tissue microenvironment, the stem cell niche that homes them and regulates the balance between stem cell renewal and differentiation. The Drosophila male stem cell niche provides an excellent system for studying this process. Although several signaling molecules, cytoskeletal and other factors have been identified, many aspects of niche regulation and coordination of these events remain unsolved. My scientific focus is on the mechanisms and factors that regulate stem cell maintenance in the Drosophila testis and on how stem cells interact with their neighboring cells to shape the niche microenvironment. Elucidating the role of transcription factors such as the Hox genes, as well as that of the cytoskeleton and tumor suppressor genes such as dlg, scrib and lgl within the complex gene network underlying testis homeostasis are some of my main research interests.
Diagram depicting early spermatogenesis in Drosophila.
Abbreviations: CySCs, somatic cyst stem cells; GSCs, germline stem cells; SCCs, somatic cyst cells
Hox genes orchestrate male stem cell niche formation and testis morphogenesis through a battery of Hox responsive genes.
A screen for Hox responsive genes performed in the lab of Ingrid Lohmann (Hueber, 2009) identified genes with a designated function in gonad morphogenesis such as nanos, oskar, Sox100B, fasciclin III, bag of marbles (bam), zero population growth (zpg) and zinc-finger homeodomain 1 (zfh1) but also a great number of yet non-studied male niche-specific genes. These genes provide critical entry points to elucidate niche establishment and morphogenesis under the control of Hox genes. My work aims at understanding how the posterior Hox genes abd-A and Abd-B regulate the complex gene network in the male stem cell niche of Drosophila and provide insights on the striking functional conservation of homologous genes in plants and animals, and their respective stem cell niches. Elucidating conserved mechanisms of stem cell control in both lineages could reveal the importance underlying this conservation and justify the evolutional pressure to adapt homologous molecules for performing the same task (Papagiannouli & Lohmann, 2012).
Physical contacts among the cell populations in the Drosophila testis allow the exchange of signals that promote tissue survival and homeostasis.
Recent advances in spermatogenesis have shown that male stem cell niche and subsequent testis morphogenesis is achieved through the physical contact and diffusible signals exchanged between the germline and somatic cell populations. The tumor suppressor genes discs large (dlg), scribble (scrib) and lethal giant larvae (lgl) code for scaffolding proteins associated with either the septate junctions or the cytoskeleton matrix. Analysis over the last decades revealed that these proteins act as dynamic organizers, functioning during epithelial polarization, asymmetric neuroblast division, and formation of neuromuscular junctions.
My previous work, together with Bernard M. Mechler, has shown that these proteins are also required for gonad and testis integrity. Synthesis of the Scrib larger isoform in the gonadal mesoderm is independent of germ cells and occurs also in agametic valois (vls) and capsuléen (csul) embryonic gonads, whereas Scrib synthesis in germ cells requires contact to the gonadal mesoderm. Moreover, mutations in dlg and scrib may exert no major effect on the gonad coalescence but affect the internal structure of the gonads, as the gonadal mesoderm that normally extends cellular projections among the germ cells in wild type gonads is absent in these mutants (Marhold, Papagiannouli et. al., 2003). More recent work revealed a new role of dlg in the Drosophila testis, as mutations in dlg lead to testis defects and cell death. Dlg is required throughout spermatogenesis in the somatic lineage, in the somatic stem cells and cyst cells, to encapsulate the germ cells and promote their survival, growth, and differentiation (Papagiannouli & Mechler, 2009). The extensive defects in dlg testis underline the importance of the somatic cells in the establishment and maintenance of the male stem cell niche and somatic cell differentiation (Papagiannouli & Mechler, 2010). As polarity scaffolds are nowadays considered to be dynamic organizing centers of site-specific protein targeting or exclusion from adjacent domains to provide guiding cues for signaling molecules and targeted membrane insertion, studying Dlg, Scrib and Lgl in other tissue contexts including the Drosophila testis has gained new interest (Papagiannouli & Mechler, 2012).
Research papers in peer-reviewed journals
1. F. PAPAGIANNOULI (2013), The internal structure of embryonic gonads and testis development in Drosophila melanogaster requires scrib, lgl and dlg activity in the soma, Int.J.Dev.Biol. 57: 25 - 34 (doi: 10.1387/ijdb.120087fp). [PDF]
2. S. Sorge, N. Ha, M. Polychronidou, J. Friedrich, D. Bezdan, P. Kaspar, M.H, Schäfer, S. Ossowski, S.R. Henz, J. Mundorf, J. Rätzer, F. PAPAGIANNOULI & I. Lohmann (2012), The cis-regulatory code of Hox function in Drosophila, EMBO J. 31(15):3323-33 [LINK]
3. Z. Zhai, Nati Ha*, F. PAPAGIANNOULI*, A. Hamacher-Brady*, N. Brady*, S. Sorge, D. Bezdan, I. Lohmann (2012), A Genetic Framework for Apoptosis Regulation in Development and Disease, PLoS Genetics 8(3): e1002582 [PDF]
(*These authors contributed equally to the work)
4. F. PAPAGIANNOULI, B.M. Mechler (2009), discs large regulates somatic cyst cell survival and expansion in Drosophila testis, Cell Research, 10: 1139-49 [PDF]
5. Brandt, F. PAPAGIANNOULI, N. Wagner, M. Wilsch-Brauninger, M. Braun, E.E. Furlong, S. Loserth, C. Wenzl, F. Pilot, N. Vogt, T. Lecuit, G. Krohne, J. Grosshans.(2006), Developmental control of nuclear size and shape by Kugelkern and Kurzkern, Current Biology, 16: 543-552 [PDF]
6. J. Marhold*, F. PAPAGIANNOULI*, M. Li, A. Patel, B.M. Mechler (2003), Requirements for scribble expression in newly formed gonads of Drosophila embryos, Mechanisms of Development, Gene Expression patterns 3: 143-146
(*These authors contributed equally to the work) [LINK]
Review papers in peer-reviewed journals
1. F. PAPAGIANNOULI, I Lohmann (2012), Shaping the niche: lessons from the Drosophila testis and other model systems, Biotechnol J. 7(6): 723-36 [LINK]
2. F. PAPAGIANNOULI, B.M. Mechler (2010), discs large in the Drosophila testis, An Old player on a new task, Fly, 4-4: 294-298 [PDF]
1. F. PAPAGIANNOULI, B.M. Mechler (2013), Modeling tumorigenesis in Drosophila: current advances and future perspectives, Future Aspects of Tumor Suppressor Genes, Dr. Yue Cheng (Ed.), ISBN: 978-953-51-1063-7 InTech publications. [PDF]
2. F. PAPAGIANNOULI, B.M. Mechler (2012), Refining the role of Dlg, Scrib and Lgl in tumor suppression and beyond: Learning from the old time classics, chapter in „Tumor Suppressor Genes“, ISBN 978-953-307-879-3, InTech publications. [PDF]