The Role of Arx in Specification and Maintenance of Pancreatic Islet α-Cells

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Degree type
Doctor of Philosophy (PhD)
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Cell & Molecular Biology
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alpha-cells
Arx
maintenance
pancreas
specification
transdifferentiation
Cell Biology
Developmental Biology
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2014-08-22T00:00:00-07:00
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Abstract

Correct specification and maintenance of pancreatic islet cells is an intricate process. Previous studies have demonstrated the essential role transcription factors play in this process. For islet glucagon-producing alpha-cells one such transcription factor is the aristaless-related homeobox gene (Arx). Previous studies have demonstrated that Arx is necessary and sufficient for alpha-cell specification where ablation of Arx results in complete loss of the alpha-cell lineage and misexpression leads to conversion into an alpha-cell phenotype. However, the role of Arx in maintenance of alpha-cell fate as well the impact non-null mutations of Arx have on alpha-cell development has not been explored. In this dissertation, I utilize mouse models and pancreatic analysis to address this question. My results demonstrate that Arx is necessary to maintain alpha-cell fate during development as well as in the adult. Furthermore, analysis of a non-null expansion mutation of Arx suggests dual roles for this factor during alpha-cell specification in activation of alpha-cell fate and repression of non-alpha-cell fate. These findings expand the role of Arx in the islet alpha-cell as well as provide an attractive avenue for future therapies for type II diabetes.

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Catherine L. May
Date of degree
2013-01-01
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