Multicellularity is based on cell communication for the correct allocation of call fates and the maintenance of tissue homeostasis. We study cellular behaviour in the context of developing animal tissues trying to understand how external signals interface with cell-intrinsic processes, primarily transcription. Our main areas of focus are: (a) the transcriptional regulation of neural development and (b) the mechanism of Notch activation by its ligands. Our main model system is Drosophila melanogaster. bHLH transcription factors play crucial roles in the specification of neural precursors. We study bHLH proteins belonging to two classes: the proneural activators and the "Orange" (or HES) repressors. Although these two classes recognize different DNA target sites, they often regulate the same enhancers. We have identified a mechanism for this, namely the recruitment of bHLH-Orange repressors [E(spl) proteins] on target genes via protein-protein interaction with proneural bHLH activators (Da and Sc). We have recently turned our attention towards another bHLH-Orange factor, Hey, which participates in a different process, namely the differentiation of nascent neurons.

Both Hey and the complex of seven E(spl) genes are transcriptional targets of Notch (in their respective contexts, as noted above). We are studying how Notch signalling is sequentially redeployed in various instances of neural development. Among other approaches, we have initiated a mechanistic study of how the two ligands of Notch, Delta and Serrate, activate their receptor. We have found that association with either of two E3-ubiquitin-ligases, Neuralized or Mindbomb, is a prerequisite for Delta/Serrate activity. We are currently studying ubiquitylation by these enzymes and how it correlates with Delta/Serrate trafficking and signalling activity.

Selected Publications

Monastirioti, M., Giagtzoglou, N,. Koumbanakis, K.A., Zacharioudaki, E., Deligiannaki, M., Wech, I., Almeida, M., Preiss, A, Bray, S. and Delidakis, C. (2010) Drosophila Hey is a target of Notch in asymmetric divisions during embryonic and larval neurogenesis. Development 137: 191-201.

Pitsouli, C. and Delidakis, C. (2005) The interplay between DSL proteins and ubiquitin ligases in Notch signaling. Development 132: 4041-4050.

Giagtzoglou, N., Koumpanakis, K.A., Fullard, J.F., Zarifi, I. and Delidakis, C. (2005) Role of the Sc C-terminus in transcriptional activation and E(spl) repressor recruitment. J. Biol. Chem. 280: 1299-305.

Giagtzoglou, N., Alifragis, P., Koumbanakis, K.A. and Delidakis, C. (2003) Two modes of recruitment of E(spl) repressors onto target genes. Development 130: 259-270.

Pavlopoulos, E., Pitsouli, C., Klueg, K., Muskavitch, M.A.T., Moschonas, N.K. and Delidakis, C. (2001) Neuralized encodes a peripheral membrane protein involved in Delta signalling and endocytosis. Dev. Cell 1: 807-816.