ETD

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Tesi etd-06112013-172052


Tipo di tesi
Tesi di laurea magistrale
Autore
SIMULA, LUCA
URN
etd-06112013-172052
Titolo
Analysis of Xhmga2 in the gene network of neural crest in Xenopus laevis
Dipartimento
BIOLOGIA
Corso di studi
BIOLOGIA MOLECOLARE E CELLULARE
Relatori
relatore Prof. Vignali, Robert
Parole chiave
  • HMGA
  • chromatin remodeler
  • epithelial-mesenchymal transition
  • neural crest
  • Xenopus
Data inizio appello
18/07/2013
Consultabilità
Non consultabile
Data di rilascio
18/07/2053
Riassunto
Neural crest cells are a cell population able to undergo an epithelial-to-mesenchymal transition (EMT) during the embryonic development of all vertebrates. For this reason, they represent a good model for the in vivo study of EMT, which also characterizes the metastatic transformation of tumor cells. In particular, several genes re-expressed by tumor cells during the EMT process (Slug, Snail, Twist), are the same that drive the normal EMT process of neural crests in the developing embryo. Several evidences have shown an involvement in EMT regulation also for HMGA proteins (HMGA1 and HMGA2), small protein of about 100 amino acids that are able to bind AT-rich DNA stretches through domains defined AT-hooks, thus modifying the local chromatin conformation and contributing in this way to regulate gene transcription. HMGA factors are involved in the expression of these EMT-related genes, as shown by in vitro studies on tumor cells. In our laboratory, the function of the unique homolog of this family, Xhmga2, in the frog Xenopus laevis has been investigated. The expression of this gene has been described in the developing neural crest population and its role in the expression of genes involved in EMT-process like Xslug and Xtwist has been approached. The aim of my thesis work has been to clarify the roles and the hierarchical relationship of XHMGA2 within the gene network that specifies the fate of these cells and their subsequent EMT and migration. The data obtained have allowed to characterize Xmsx1 as a key transcription factor involved in regulating Xhmga2 expression both in the neural crest cells and in the dorsal neural tube. It has also been shown that the modulation of Xhmga2 levels by the WNT and BMP signaling pathways is critically mediated by Xmsx1, although another Wnt-dependent factor could be involved, in cooperation with Xmsx1, in Xhmga2 regulation at the neural plate border. Subsequently, it has been performed a comparative analysis of the effects of Xhmga2 and Xmsx1 over-expression and down-regulation on the expression of several neural crest Xmsx1-regulated genes (Xpax3, Xslug, Xtwist). By combining multiple injections, it has been possible to define the role of Xhmga2 in the expression of EMT-related genes: our data indicate that, once expressed in the neural crest territories, Xhmga2 is not at all involved in the regulation of neural plate border genes, like Xmsx1 itself and Xpax3, but is required for allowing these genes to promote the expression of neural crest specifier genes like Xslug and Xtwist, which in turn are required for the EMT process. Finally the role of Xhmga2 in proliferation of neural crest cells has been investigated through modulation of its levels of expression and detection of proliferative rate; our conclusion is that Xhmga2 is not involved in modulating neural crest cells proliferation rate during early development.
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