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Title: The role of TBX22 in craniofacial development
Author: Hoshino, A.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2011
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Cleft lip and/or cleft palate are a heterogeneous group of disorders that rank among the commonest birth defects known, affecting 1 in 700 births worldwide. The underlying cause is poorly understood, with a complex interaction of genes and environmental factors being implicated. Nevertheless, several important genetic causes have been identified, including that of X-linked cleft palate and ankyloglossia (CPX). CPX is a semi-dominant condition caused by mutations in TBX22 which encodes a T-box containing transcription factor. TBX22/Tbx22 is highly conserved and expressed in the developing palatal shelves as well as at the base of the tongue, medial and lateral nasal prominences and periocular mesenchyme in both human and mouse embryos. This project set out to better understand the functional role of TBX22 using Tbx22 null mouse model that is characterised by overt or submucous cleft palate, ankyloglossia and choanal atresia. Microarray analysis of E13.5 palatal shelves dissected from wild type and Tbx22 null mice revealed a global upregulation of muscle genes such as myosin and muscle actin in the null palatal shelves. Key myogenic regulatory factors MyoD and myogenin were moderately upregulated. Increased expression was independently confirmed using real-time PCR. In vitro analysis in a mammalian cell line using luciferase reporter assays and chromatin immunoprecipitation showed that TBX22 could repress the MyoD promoter and was capable of interacting with its promoter regions. This may provide a link between lack of Tbx22 and upregulation of muscle markers. These results support a hypothesis that MyoD is a possible direct target gene of TBX22. In addition, decreased cell proliferation in the Tbx22 null palatal shelves was observed, along with reduced expression of Cyclin D2. This indicates that TBX22 has a role in the regulation of cell proliferation during palate development as well as a previously identified role in osteoblast differentiation and maturation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available