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Title: Gut development : the regulation, evolution and function of Bapx1
Author: Wright, Alison Julia
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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The regulatory elements responsible for directing tissue-specific Bapx1 expression have not yet been determined, therefore to pursue investigation of the role of the mesenchyme in gut development would require elucidation of a gut-specific Bapx1 enhancer. Comparative sequence analysis between human, mouse and fish identified two candidate control elements, termed ProxB and DistB, which residue 11kb and 18kb respectively downstream of Bapx1. ProxB constitutes a short region of high sequence conservation between human and mouse, within which 180bp was also found to be conserved to zebrafish. DistB encompasses a more extensive 8kb genomic region highly conserved in mammals. Both the ProxB putative regulatory element and a 2kb subfragment of DistB named DistB1 were cloned into a LacZ reporter construct and assayed for enhancer activity in transgenic mice. Both elements exhibited tissue-specific enhancer capacities with ProxB-driven expression initially confined to the mandibular portion of the first branchial arch and later detected in Meckel’s cartilage and the middle ear. Detailed analysis of the expression pattern and comparison to evolutionarily conserved expression domains provides good evidence that ProxB constitutes a region-specific Bapx1 regulatory element. DistB1 appears to be capable of directing expression to several different tissues, notably including the digits where it closely resembles endogenous Bapx1 expression. Further parallels between the DistB1 and Bapx1 expression domains suggest that this element may also contribute to the endogenous regulation of Bapx1. Phenotypic comparisons between Bapx1 null mutant mice and their wildtype counterparts have contributed significantly to knowledge of the wildtype function of the gene. Within the developing gut, distinct molecular boundaries are apparent. Bapx1 demarcates the domain of the posterior stomach and asplenic null mutants attest to its being essential for formation of the spleen. Various gut markers were employed to study the disruption of both gut development and defined molecular domains in the absence of Bapx1.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available