Impaired pancreatic development in Hif2-alpha deficient mice |
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Authors: | Huiping Chen Golbahar Houshmand Sanjay Mishra George K. Gittes |
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Affiliation: | a Division of Pediatric General and Thoracic Surgery, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, One Children’s Drive, 4401 Penn Avenue, Rangos Research Center, Pittsburgh, PA 15244, United States b Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, United States c Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261, United States |
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Abstract: | Accumulating data suggest the existence of a link between hypoxia and maintenance of the undifferentiated cell state, but little is known about the cellular signaling mechanisms underlying this process. Recent reports reveal a direct link between components of the hypoxia signaling pathway and Notch pathway in maintaining precursor cells in an undifferentiated state. Here, we report that in the developing mouse pancreas, Hif2-α is expressed in pancreatic progenitor cells, but its expression is lost in committed endocrine progenitors as well as in differentiated endocrine and exocrine cells. In an attempt to analyze the function of HIF2-α in the developing pancreas, we studied Hif2-α−/− pancreas. Our analyses revealed that in addition to the decreased size and branching, the Hif2-α deficient pancreas also displayed impaired notch signaling and cell differentiation. Finally, we found that HIF2-α binds directly to Notch-IC and that the responsible site for this interaction is within the RAM domain of Notch protein. These results suggest that HIF2-α is required for normal mouse pancreatic development. |
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Keywords: | Pancreas Development Differentiation Notch signaling Mouse |
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