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Christos Delidakis
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.
Kux, K, Kiparaki, M and Delidakis, C. (2013) The two Tribolium E(spl) genes show evolutionarily conserved expression and function during embryonic neurogenesis. Mech. Dev. 130: 207-225.
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.
Cooper M.T.D., Tyler D., Furriols M., Chalkiadaki A., Delidakis C. and Bray S. 2000. Spatially restricted factors co-operate with Notch in the regulation of Enhancer of split genes. Dev. Biol. 221, 390-403.
Nagel A.C., Apidianakis Y., Wech I., Maier D., Delidakis C. and Preiss A. 2000. Neural hyperplasia induced by RNA interference with m4/ma gene activity. Mech. Dev. 98, 19-28.
Apidianakis, Y., Grbavec, D., Stifani, S. and Delidakis, C. 2001. Groucho mediates a Ci-independent mechanism of hedgehog repression in the anterior wing pouch. Development 128, 4361-4370.
Boutla, A., Delidakis, C., Livadaras I., Tsagris, M. and Tabler, M. 2001. Short 5’-phosphorylated double-stranded RNAs induce RNA interference in Drosophila. Curr. Biol. 11, 1776-1780.
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
Pavlopoulos, E., Kokkinaki, M., Koutelou, E., Mitsiadis, T.A., Prinos, P., Delidakis, C., Kilpatrick, M.W., Tsipouras, P., Moschonas, N.K. 2002. Cloning, chromosomal organization and expression analysis of Neurl(1), the mouse homolog of Drosophila melanogaster neuralized gene. Biochim Biophys Acta 1574, 375-82.
Parkhurst, S.M. and Delidakis, C. 2002. Fly Developments: an introspective. (review) Bioessays 25, 87-89.
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.
Boutla, A., Delidakis, C. and Tabler, M. 2003. Developmental defects by antisense-mediated inactivation of micro-RNAs 2 and 13 in Drosophila and the identification of putative target genes. Nucleic Acids Res, 31, 4973-4980.
Boutla, A., Delidakis, C., Livadaras, I., and Tabler, M. 2003. Variations of the 3' protruding ends in synthetic short interfering RNA (siRNA) tested by microinjection in Drosophila embryos. Oligonucleotides, 13, 295-301.
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.
Pitsouli, C. and Delidakis, C. 2005. The interplay between DSL proteins and ubiquitin ligases in Notch signaling. Development 132, 4041-4050.
Acar, M., Jafar-Nejad, H., Giagtzoglou, N., Yallampalli, S., David, G., He, Y., Delidakis, C. and Bellen, H.J. 2006. Senseless physically interacts with proneural proteins and functions as a transcriptional co-activator. Development 133 , 1979-89.
Glittenberg, ? ., Pitsouli, C., Garvey, C., Delidakis, C. and Bray, S. 2006. Role of conserved intracellular motifs in Serrate signalling, cis-inhibition and endocytosis. EMBO J . 25 , 4697–4706
Bejarano, F., Perez, L., Apidianakis, Y., Delidakis, C. and Milan , M. 2007. Hedgehog restricts its expression domain in the Drosophila wing. EMBO Reports 8 , 778-783
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
Daskalaki, A., Shalaby, N.A., Kux, K., Tsoumpekos, G., Tsibidis, G.D., Muskavitch, M.A.T. and Delidakis C. 2011. Distinct intracellular motifs of Delta mediate its ubiquitylation and activation by Mindbomb1 and Neuralized. . J. Cell Biol. 195, 1017-1031
Zacharioudaki, E., Magadi, S. S. and Delidakis, C. 2012. bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation. Development 139, 1258-69
Zarifi I, Kiparaki M, Koumbanakis KA, Giagtzoglou N, Zacharioudaki E, Alexiadis A, Livadaras I, Delidakis C. 2012. Essential roles of Da transactivation domains in neurogenesis and in E(spl)-mediated repression. Mol Cell Biol. 32: 4534-48
Kux, K, Kiparaki, M and Delidakis, C. 2013. The two Tribolium E(spl) genes show evolutionarily conserved expression and function during embryonic neurogenesis. Mech. Dev. 130: 207-225