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Title: Molecular regulation of cell fate choice in the developing mesoderm
Author: Moreno-Fortuny, Artal
ISNI:       0000 0004 7658 2799
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2018
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The molecular processes underlying fate cell decision of mesoderm progenitors are not fully understood yet. Here two different mesoderm-derived cell types are studied to gain information about how these differentiation processes are regulated. On the one hand, embryonic myoblasts are used to elucidate the transcriptional mechanisms that govern the capacity of Delta-like Notch canonical ligand 4 (DLL4) to block myogenesis and to induce the start of a new transcriptional program. I show that DLL4 induces global chromatin opening that results into a more permissive transcriptional framework. Data suggest that the chromatin remodelling might be happening through transcriptional activation of PR domain zinc finger protein 1 (PRDM1). Chromatin opening leads to these cells being able to express markers for different cell types without ever committing to those fates. One the other hand, the multipotent 10T1/2 cell line has been used to interrogate the role of the melanoma cell adhesion molecule (MCAM), one gene up-regulated by DLL4, in the differentiation process towards myogenesis and chondrogenesis. Unexpectedly data here presented shows that loss of MCAM influences differentiation by affecting proteins related to the planar cell polarity pathway rather than through canonical WNT.
Supervisor: Kimber, Susan ; Cossu, Giulio Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available