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Title: The role of Tbx18 in axial mesoderm development
Author: Burbridge, Sarah
ISNI:       0000 0004 2735 727X
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2012
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The axial mesoderm is a specialised population of cells lying at the midline of the embryo. It is composed of two cell populations: the anterior prechordal mesoderm (PM), bounded posteriorly by the notochord (NC). A wealth of studies have shown that both PM and NC are key organising centers that pattern and regionalise the overlying neuroectoderm into fore-, mid-, hindbrain and spinal cord. However, it is unclear how the axial mesoderm becomes regionalised into PM and NC with a sharp boundary established between the two domains. Here I use the chick embryo to address this question. One of the reasons that studies into the development of axial mesoderm have been hampered is due to the lack of an exclusive marker of the PM. Here, I show that Tbx18 is a novel and exclusive marker of the PM and is expressed once the axial mesoderm has fully extended. Much emphasis has been placed in the literature upon the importance of Nodal signalling in axial mesoderm formation, however, little is known about its role in the fully extended axial mesoderm. Here, I show that Nodal initiates Tbx18 expression in the fully extended axial mesoderm, i.e. acting to further specify PM. My studies reveal, further, that Nodal signalling is inhibited by the paraxial mesoderm and retinoic acid. Together, the antagonistic signals appear to establish the posterior limit of the PM and the anterior limit of the NC. Finally, I find that Tbx18 sharpens the PM-NC boundary by downregulating the NC marker 3B9 and establishing a third subpopulation of Shh- axial mesoderm that lies at the PM-NC interface. I discuss the potential significance of this third axial mesoderm population.
Supervisor: Placzek, Marysia Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available