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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 440-445 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 399 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 2010 |
| Externally published | Yes |
Funding
The authors would like to thanks Dr. F.J. Gonzalez for providing us with the Arnt-loxP strain, and also the Concern Foundation (FE), The Cochrane-Weber endowed Fund in Diabetes Research (FE), the NIH (GKG), Pennsylvania State Tobacco Fund (GKG), and the Children’s Hospital of Pittsburgh for financial support. We would also like to thank Drs. S.D. Leach, B. Ghosh and C. Simone for providing us with the Notch-IC, δNotch-IC, Hif1-α, and Hif2-α constructs.
Keywords
- Development
- Differentiation
- Mouse
- Notch signaling
- Pancreas
ASJC Scopus subject areas
- Molecular Biology
- Biophysics
- Biochemistry
- Cell Biology