Functional Characterization Of Rfx6 And Sel1L In Pancreatic Development
During vertebrate embryonic development, a common pool of progenitor cells gives rise to all three lineages of the pancreas, including endocrine, exocrine and duct cells. The molecular mechanisms regulating pancreatic differentiation are incompletely understood. We investigated the function of two genes in the control of pancreatic differentiation. In chapter two, we show that Sel1L (Sel-1 suppressor of lin12-like) is a potential Notch regulator during pancreas development. SEL1L is initially expressed throughout the pancreatic epithelia and later restricted in differentiated cells. Mice lacking SEL1L show severe defects in the differentiation of both endocrine and exocrine pancreas. These differentiation defects can be rescued by the Notch signaling inhibitor, DAPT. In chapter three, we show that RFX6 (Regulatory factor X 6) functions as a transcription factor in the developing pancreas. Knockdown of RFX6 in zebrafish causes disorganized pancreatic morphology and attenuated insulin expression. Expression of Nkx6.1 is down regulated in pancreatic cell line transfected with Rfx6 SiRNA. Luciferase reporter studies reveal that RFX6 activates the proximal promoter of Nkx6.1. In summary, our studies have provided new insight in the spatial and temporal regulation underlying pancreas development.
dissertation or thesis