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(in English) Post-implantation embryo development proceeds through several key morphogenetic events that are fine-tuned by epigenetic modifications. Gastrulation is one of the most crucial developmental event that occurs during early post-implantation stage resulting in the formation of the three germ layers together with the establishment of the anterior-posterior (A-P) axis. It requires a highly coordinated interaction between the embryonic and extra-embryonic regions of the developing embryo. Gastrulation initiates with the formation of the primitive streak and, during which, cells of the epiblast delaminate and ingress through the primitive streak to form the mesoderm and definitive endoderm. During early post-implantation stages, the pluripotent cell population of the epiblast undergoes very rapid cellular proliferation and extensive epigenetic programming. There are numerous studies emphasizing various signaling molecules, transcription factors and epigenetic machinery maintaining the genomic stability that drive successful gastrulation and any discrepancy or defects almost always results in embryonic lethality. One such newly highlighted silencing machinery is that of the Human silencing hub (HUSH) complex comprising of the core members; FAM208A; H3K9me3-reader, MPP8 and PPHLN that together...

(ENGLISH) Ubiquitin signaling is a key regulatory mechanism for many important cellular processes such as transcription, differentiation and cell division. Cell division requires duplication of all genetic material during S-phase followed by its precise partitioning between two daughter cells during mitosis. Misregulation of the complex mitotic machinery may lead to aneuploidy and genomic instability, known drivers of tumorigenesis. Indeed, systematic genetic analysis of many cancer tissues over the last decades, indicates the presence of severe chromosome abnormalities in thousands of cancer tissue samples. In this work, I investigated the function of two components of ubiquitin signaling, the deubiquitinating enzyme UCHL3 and the E3 ubiquitin ligase TRIM15. The hypothesized role of E3 ligase TRIM15 in the cell cycle regulation could not be confirmed by our experiments, but I observed an effect on cell adhesion and motility instead. UCHL3 was identified using high-content visual siRNA screen, as a critical factor controlling genome segregation and integrity. Interestingly, it has been previously reported that UCHL3 levels are altered in various cancer types, especially colon cancer. My data demonstrate that UCHL3 drives proper alignment of chromosomes at the metaphase plate by facilitating...

Includes bibliographical references (p. 105-114). Number of sources in the bibliography: 117 Thesis (Ph. D.) -- University of Cyprus, Faculty of Pure and Applied Sciences, Department of Biological Sciences, 2013. The University of Cyprus Library holds the printed form of the thesis. Η γαστριδίωση, η οποία προηγείται της οργανογένεσης είναι μια από τις πιο σημαντικές διαδικασίες κατά την εμβρυογένεση. Ξεκινά με την δημιουργία της αρχικής λωρίδας (primitive streak, PS) κατά την εμβρυονική μέρα 6.5 προκειμένου να δημιουργηθούν οι τρεις εμβρυονικές στοιβάδες: το μεσόδερμα, το ενδόδερμα και το εξώδερμα. Για την έναρξη της γαστριδίωσης χρειάζονται σήματα τα οποία προέρχονται από τους δύο εξωεμβρυονικούς ιστούς: το σπλαχνικό ενδόδερμα (visceral endoderm) το οποίο αποτελεί πρόγονο ιστό του αμνιακού σάκου και συμβάλλει στη δημιουργία του ενδοδέρματος και το εξτραεμβρυονικό εκτόδερμα (ΕΧΕ) το οποίο είναι ο πρόγονος ιστός του μεγαλύτερου τμήματος του πλακούντα που ονομάζεται τροφοβλάστη. Παρόλο που έχει δειχθεί ότι σήματα τα οποία προέρχονται από το εξτραεμβρυονικό εκτόδερμα χρειάζονται για την έναρξη της γαστριδίωσης, παραμένει άγνωστο κατά πόσο αυτά τα σήματα επηρεάζουν την πορεία της γαστριδίωσης. Ο κύριος στόχος αυτής της διατριβής είναι η χρησιμοποίηση knockout ποντικών για το γονίδιο Εts2, τα ονομαζόμενα Εts2 type-II mutant έμβρυα για τον προσδιορισμό νέων επιδράσεων του ΕΧΕ στις διαδικασίες τις γαστριδίωσης μετά την έναρξη της. Τα αποτελέσματα μας έχουν δείξει για πρώτη φορά ότι ότι τα σήματα που προέρχονται από το ΕΧΕ χρειάζονται για την συνέχιση της γαστριδίωσης στα έμβρυα αφού επηρεάζει: την επιμύκηνση του PS, την ολοκλήρωση της μετατροπής των PS επιθηλιακών κυττάρων σε μεσεγχυματικά (EMT), καθώς και την ανάπτυξη παραγώγων του PS όπως για παράδειγμα του node. Παρουσιάζονται αποδείξεις και προτείνουμε ένα μοντέλο το οποίο παρέχει μια γενετική εξήγηση για το πώς η έκφραση του Ets2 στο EXE, ρυθμίζει αυτά τα γεγονότα. Gastrulation, a prerequisite for organogenesis, is one of the most fundamental aspects of embryogenesis. During gastrulation the initially amorphous one-layered and unpatterned epiblast transforms into a fully patterned three-layered entity that allows correct organogenesis to take place. Gastrulation begins with the formation of the Primitive Streak (PS), at the posterior side of the epiblast, which in mice starts 6.5 days after fertilization (E6.5). Mammalian gastrulation requires signals from two extraembryonic tissues: the visceral endoderm (which is the progenitor of yolk-sac endoderm and also contributes to the formation of the definitive endoderm) and the extraembryonic ectoderm (EXE) trophoblast (progenitor of placental trophoblast). Although EXE trophoblast signals the embryo for PS initiation, it is unknown whether it also signals for the progression of gastrulation after PS initiation. The main focus of this project was to use homozygous gene knockout mice for the transcription factor Ets2 (the Ets2 type-II mutants) as an in vivo model for discovering, new fundamental gastrulation events after gastrulation initiation that require EXE trophoblast signaling. We show for the first time that trophoblast signalling is required in vivo for fundamental events during gastrulation such as: PS elongation, completion of intraembryonic mesoderm epithelial–mesenchymal transition (EMT) and the development of anterior primitive streak derivatives such as the node. We present evidence and propose a model that provides a genetic explanation as to how Ets2-dependent EXE trophoblast signaling mediates these events within the epiblast.