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Title: FGF signalling in the control of craniofacial and tracheal gland development
Author: May, Alison Judith
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2015
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The submucosal glands (SMGs) of the respiratory system are specialized structures essential for maintaining airway homeostasis. The significance of SMGs is highlighted by their involvement in respiratory diseases such as cystic fibrosis and asthma, where their phenotype and function are severely altered. Uncovering the normal development of the airway SMGs is essential to elucidate their role in these disorders, however, very little is known about their morphogenesis. To begin to understand the mechanisms involved in their arborisation, the development of the nasal SMGs was investigated, with glands being categorised into different subsets based on their locations and methods of development. We also used these heterogeneous nasal glands as a model to investigate the process of lumen formation within gland ducts. Due to the imperative role of FGF signalling during the development of other branched structures, we investigated the role of Fgf10 during the branching morphogenesis of the nasal SMGs. In the Fgf10 null embryo, some nasal SMGs were absent while others showed normal duct elongation but defective branching, indicating that different glands require Fgf10 for selective stages of development. Furthermore, certain SMGs present in the Fgf10 homozygote were missing in the Fgfr2b mutant, suggesting compensation by another FGF ligand. In Fgf10 heterozygous mice the tracheal glands were reduced in size at an early age, with an altered A/P distribution of the SMGs postnatally, a deficit in glands that was not recovered in adults. The functional consequence of the reduction of SMGs in adult heterozygotes was investigated and showed that tracheal SMGs in Fgf10 mutant mice produce less mucus. Considering this, we assessed the ability of mutant mice to respond to respiratory challenges. We also analysed the defective salivary gland phenotype of Fgf10 heterozygotes and showed that gland dysplasia gave rise to a reduction in saliva output.
Supervisor: Tucker, Abigail Saffron ; Noble, Alistair Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available