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Identifier uch.biology.phd//2004giagtzoglou
Title Μελέτη bHLH-Orange πρωτεϊνών στη Drosophila melanogaster: Α) Τρόπος δράσης των E(spl) γονιδίων κατά τη νευρογένεση Β) Ανάλυση του προτύπου έκφρασης του γονιδίου Hey και της σχέσης του με το σηματοδοτικό μονοπάτι Notch
Alternative Title Study od bHLH orange proteins in drosophila melanogaster: a) mode of action of E (spl) proteins during neurogenesis, b) analysis of the pattern of expression of hey and its relationship with notch signalling pathway
Author Γιαγτζόγλου, Νικόλαος
Thesis advisor Δελιδάκης, Χρήστος
Abstract A) Neurogenesis in all animals is triggered by the activity of a group of bHLH transcription factors, the proneural proteins [i.e. Achaete (Ac) and Scute (Sc)], whose expression endows ectodermal regions with neural potential. The eventual commitment to a neural precursor fate involves the interplay of these proneural transcriptional activators with a number of other transcription factors, which fine-tune transcriptional responses at target genes. Most prominent among the factors antagonizing proneural protein activity are the HES [E(spl)] bHLH proteins. We show here that E(spl) proteins m7 and mγ are potent inhibitors of neural fate, even in the presence of excess Sc activity and even when their DNA-binding basic domain has been inactivated. Furthermore, these E(spl) proteins can efficiently repress target genes that lack cognate DNA binding sites, as long as these genes are bound by Ac/Sc activators. This activity of E(spl)m7 and mg correlates with their ability to interact with proneural activators, through which they are probably tethered on target enhancers. The co-repressor Groucho is always needed for target gene regulation. In addition, by using in vivo and in vitro assays we have discovered that the N-teminal region (including the bHLH domain) of E(spl)m7 interacts with the C-teminal domain of Sc. An important dual role for the Sc C-terminal domain is shown: on one hand it acts as a transcription activation domain and on the other it is used to recruit E(spl) proteins. In vivo, the Sc C-terminal domain is required for E(spl) recruitment in an enhancer-context dependent fashion, suggesting that in some enhancers alternative interaction surfaces can be used to recruit E(spl) proteins. As far as E(spl)m7 is concerned, the integrity of the Orange domain is important for in its activity. Analysis of reporter genes and sensory organ (bristle) patterns reveals that, in addition to this indirect recruitment of E(spl) onto enhancers via protein-protein interaction with bound Ac/Sc factors, direct DNA binding of target genes by E(spl) also takes place. B) E(spl) proteins belong to a family of bHLH proteins, called bHLH-Orange proteins. All members of this family share homology with respect to a region called the Orange domain, which is considered to play an important role in the regulation of the proteins’ intra- and intermolecular interactions and possibly thereby of their activity. Computational analysis of the Drosophila genome has shown that there are 13 representative members of this family. We were particularly interested in Hey protein. Hey protein belongs to a subgroup of bHLH-Orange proteins with distinct, evolutionarily conserved structural characteristics. Hey genes have been studied extensively in vertebrates and they have been shown to participate in numerous developmental processes such as angiogenesis and neurogenesis. They have also been shown to be novel targets of Notch signalling. Hey proteins are heterodimeric partners of Hes proteins, with which they co-operate to achieve a more efficient transcriotional repression of target genes. However, nothing is known about the corresponding gene in Drosophila. We have studied its expression pattern in various tissues and developmental stages. It has been revealed that it is always expressed in a subset of postmitotic neurons. Its expression pattern persists even after Notch signalling is seriously reduced, suggesting (at least under the present experimental conditions) that it is possibly not a target of the Notch pathway.
Language Greek
Subject bHLH orange πρωτεϊνες; E (spl) πρωτεϊνες; Hey πρωτεϊνες; Notch σηματοδοτικό μονοπάτι; Νευρογένεση
Issue date 2004-10-04
Date available 2005-01-12
Collection   School/Department--School of Sciences and Engineering--Department of Biology--Doctoral theses
  Type of Work--Doctoral theses
Permanent Link https://elocus.lib.uoc.gr//dlib/b/3/d/metadata-dlib-2004giagtzoglou.tkl Bookmark and Share
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