In my thesis I have investigated the role of the two different mechanism of epigenetic silencing: Methyl-CpG binding protein-dependent repression and chromatin remodelling activity in the neural stem cell system. I hypothesised firstly, that MeCPs may have a redundant role in neural stem cell function. Secondly, that the effect of lacking Mdb3 in neural stem cells may be different and more severe that the absence of the methyl-CpG binding proteins. The approach to investigate these hypothesis consisted on a first stage in the study of the neuroectoderm differentiation capacity of ES cells lacking one MeCP, Kaiso, following by study the function of neural stem cell (NS) lines derived from the cortex of mice lacking the MeCPs Kaiso, MeCP2 and Mbd2. I have found no defects in proliferation or self-renewal of triple null NS cells. Additionally, although triple null NS cells present a normal astrocyte differentiation, they present a delay in neuronal differentiation, defect that is only visible at early differentiation stages. Therefore, these proteins are dispensable for viability and differentiation of NS cells <i> ex vivo. </i>In contrast, I have found that Mbd3 is important for differentiation of neuroectoderm in culture, as Mbd3 null ES cells differentiate into neurons at very low frequency but do not differentiate into astrocytes. Moreover, Mdb3 is essential for establishment and/or maintenance of ES cell-derived NS cell lines. Thus while there is no evidence for a role of three MeCPs in NS cell maintenance or differentiation, the activity of the NuRD co-repressor complex is important for both properties.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:642291 |
| Date | January 2006 |
| Creators | Martin Caballero, Isabel |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/12579 |
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