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Functional role of Islet1 in pancreatic development
Malfatti, Jessica ; Pavlínková, Gabriela (advisor) ; Krausová, Michaela (referee)
1 Abstract Diabetes mellitus is characterized by the dysfunction and reduction of insulin-producing cells, resulting in hyperglycemia, which in long term harms the organism. For future therapy, it is crucial to understand the function of various factors participating in the differentiation and maturation of endocrine pancreatic cells. The aim of this study was to unravel the functional role of ISL1 during the development of the pancreas. ISL1 is expressed in all endocrine cells of the islets of Langerhansbut its function remains unclear, especially during early pancreatogenesis. As the global deletion of this gene is embryonically lethal, we used the tissue specific deletion of Isl1 in Neurod1 possitive cells using the Cre-loxP system. In this work we studied the effect of this deletion on the structure of islets of Langerhans, the formation of endocrine cell types and relative expression of genes during early pancreatic development. A defective achitecture of islets together with postnatal absence of α-cells was found in the Isl1 deletion mutant. Also, the expression of genes important for the specification of α-cell lineage and their subsequent function was decreased. The secondary outcome was the optimalization of a protocol for effective sorting of endocrine cells using fluorescent flow cytometry, which...
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Specification and differentiation of cells in pancreatic development
Malfatti, Jessica ; Pavlínková, Gabriela (advisor) ; Horáková, Olga (referee)
Pancreas is divided into exocrine and endocrine tissue. The exocrine part contains acinar cells, which produce digestive enzymes, and ductal cells that help with their transportation to the duodenum. The islets of Langerhans form the endocrine part and consist of 5 types of cells; α, β, δ, ε, and PP-cells, producing hormones glucagon, insulin, somatostatin, ghrelin and pancreatic polypeptide, respectively. Pancreas development is divided into primary, secondary and tertiary transition. Many transcription factors participate in the cell specification and differentiation processes. Pancreatic duodenal homeobox 1 specifies the pancreatic domain in primary transition. Pancreas-specific transcription factor 1A is important for the specification and differentiation of acinar cells. All endocrine cell precursors express Neurogenin 3, a key specification factor of endocrine cells. A large number of transcription factors regulate differentiation of endocrine cells as well as their function. Absence or dysfunction of some transcription factors have been associated with pathologies, for example diabetes mellitus, pancreatic carcinoma or pancreatitis. Key words Pancreas, islets of Langerhans, insulin, glucagon, development, differentiation, diabetes
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