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Title: Lineage and molecular analysis of thymus organogenesis
Author: Gordon, Julie
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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The current literature describes two conflicting hypotheses regarding the embryonic origin of the TE. The first aim of this thesis was to clarify the role of the pharyngeal ectoderm in thymus organogenesis using two independent experimental approaches. Firstly, direct assessment via a lineage analysis found no evidence for physical ectodermal contribution to the TE. Secondly, an ectopic grafting model indicated that pharyngeal endoderm was sufficient to form a normal thymus. The molecular mechanisms underlying thymus development were investigated via in situ hybridisation of candidate genes. These studies demonstrated i) Bmp2 and Bmp4 expression at the ventral tip of the third pharyngeal pouch, suggesting a role in the initiation of TE morphogenesis ii) Foxn1 and Gcm2 in specific regions within the common primordium, indicating delineation of thymus and parathyroid domains prior to organ formation, iii) restricted expression of Ehox, a novel paired-like homeobox-containing gene, in the pharyngeal endoderm prior to the onset of Foxn1 expression, suggesting it may identify prospective thymic epithelial cells. To test this, a technique for the rapid assay of gene function during thymus organogenesis was established, which utilised a novel whole embryo culture system in conjunction with in vivo electroporation of morpholino oligonucleotides. Initial proof-of-concept experiments using this technique achieved successful knockdown of Fox1 gene function in cells of the third pharyngeal pouch. In conclusion, the work presented here provides definitive evidence for a single endodermal origin for the thymic epithelium and demonstrates the existence of predetermined organ domains within the third pharyngeal pouch. It also establishes a novel technique for further investigation of the molecular mechanisms underlying early thymus organogenesis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available