Date of Award


Degree Type


Degree Name

Master of Science


Physiology and Pharmacology


Dr. Rennian Wang

Second Advisor

Dr. Stephen Sims

Third Advisor

Dr. Geoff Pickering


βl integrin and collagen matrix interactions regulate cell survival by associating with FAK and initiating MAPK/ERK signaling, but little is known about these pathways during human fetal islet ontogeny. This study investigated whether βl integrin/FAK activation of the MAPK/ERK pathway is involved in regulating human fetal islet cell survival and expression of endocrine cell markers. Isolated human fetal islet-epithelial cell clusters pre-treated with an anti-βl integrin antibody and cultured on type I collagen showed decreased cell spreading and increased cell death. Blockade of βl integrin induced a disorganization of focal adhesion contacts in the cell clusters and decreased activation of FAK and ERK1/2 leading to a reduction in PDX-1, insulin and glucagon- expressing cells, βl integrin siRNA yielded similar results. Activation of FAK increased ERK1/2 phosphorylation, as well as insulin and glucagon gene/protein expression. This study demonstrates that activation of FAK/MAPK/ERK signaling by βl integrin is required for the differentiation and survival of human fetal islet cells.



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