Cell diversification during development is guided by a handful of signaling pathways that act reiteratively to coordinate cell behavior and differentiation. How few signaling pathways generate the astonishing cell diversity during animal and organ development is the topic of our research. Capitalizing on the fact that components and mechanisms of intercellular signaling are highly conserved in evolution, we use Drosophila melanogaster (the common fruit fly) to understand the mechanisms that shape the activity of intercellular signaling in time and space. We focus on signaling by TGF-ß/BMP, a group of ligands that control a vast number of processes during development and homeostasis - from epithelial patterning to stem cell maintenance and tissue regeneration. We use a blend of techniques including genetics, genome engineering, nanobody-derived reagents, imaging and mathematical modelling to quantitatively understand the impact of cellular networks, regulatory feedback and integration of additional signalling cues on TGF-ß/BMP signaling activity and output in various contexts development and homeostasis. With Drosophila as a model, we aim at understanding the regulatory circuits that shape signaling at different biological scales: from the extracellular distribution and availability of the ligands and signal integration in the cell and the nucleus of signal-receiving cells down to the phenotypic manifestation at cellular, tissue and organismal level.

Keywords

Intercellular signaling, BMP signaling, morphogen, regulatory feedback, embryogenesis, organogenesis, epithelia, genome engineering, Drosophila, stem cells.

10 selected publications:

• AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis.
  Tracy Cai X, Li H, Safyan A, Gawlik J, Pyrowolakis G, Jasper H (2019).
  Nat Commun. 10(1):2988
• Sequence environment of BMP-dependent activating elements controls transcriptional responses to Dpp signaling in Drosophila.
  Chayengia M, Veikkolainen V, Jevtic M, Pyrowolakis G (2019).
  Development. 146(11)
• Gene regulation during Drosophila eggshell patterning.
  Pyrowolakis G, Veikkolainen V, Yakoby N, Shvartsman SY. (2017)
  Proc Natl Acad Sci USA, 114 (23), 5808-1.
• Pentagone fine-tunes glypicans to regulate multiple signaling pathways.
  Norman M, Vuilleumier R, Springhorn A, Gawlik J, Pyrowolakis G (2016).
  Elife, e13301.
• The decapentaplegic/TGF-dependent corepressor Schnurri protects epithelial cells from JNK-induced apoptosis in Drosophila embryos.
  Beira JV, Springhorn A, Pyrowolakis G, Vincent JP (2014).
  Dev Cell. 31(2) 240-47.
• Transcriptional Interpretation of the EGFR signaling gradient.
  Fuchs A, Cheung LS, Charbonnier E, Shvartsman SY*, Pyrowolakis G* (2012).
  Proc Natl Acad Sci USA. 109, 1572-77. *shared senior authorship
• Expansion-repression mechanism for scaling the Dpp activation gradient in Drosophila wing imaginal discs.
  Ben-Zvi D, Pyrowolakis G, Barkai N, Shilo BZ (2011).
  Curr Biol. 21, 1391-96.
• Control of Dpp morphogen distribution by a secreted feedback regulator.
  Vuilleumier R, Springhorn A, Patterson L, Koidl S, Hammerschmidt M, Affolter M, Pyrowolakis G (2010).
  Nat Cell Biol. 12, 611-617.
• A simple molecular complex mediates widespread BMP-induced repression during Drosophila development.
  Pyrowolakis G, Hartmann B, Muller B, Basler K, Affolter M (2004).
  Dev Cell, 7, 229-240.
• Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient.
  Müller B*, Hartmann B*, Pyrowolakis G*, Affolter M, Basler K (2003).
  Cell 113, 221-33. *equal contribution