Impaired pancreatic development in Hif2-alpha deficient mice

被引：21

作者：

Chen, Huiping ^{[1
]}

Houshmand, Golbahar ^{[1
]}

Mishra, Sanjay ^{[1
]}

Fong, Guo-Hua ^{[2
]}

Gittes, George K. ^{[1
]}

Esni, Farzad ^{[1
,3
]}

机构：

[1] Univ Pittsburgh Med Ctr, Div Pediat Gen & Thorac Surg, Childrens Hosp Pittsburgh, Rangos Res Ctr, Pittsburgh, PA 15244 USA

[2] Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Dept Cell Biol, Farmington, CT 06030 USA

[3] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 399卷 / 03期

关键词：

Pancreas; Development; Differentiation; Notch signaling; Mouse; CELL DIFFERENTIATION; ENDOCRINE DEVELOPMENT; NOTCH; MOUSE;

D O I：

10.1016/j.bbrc.2010.07.111

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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-alpha 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-alpha in the developing pancreas, we studied Hif2-alpha(-/-) pancreas. Our analyses revealed that in addition to the decreased size and branching, the Hif2-alpha deficient pancreas also displayed impaired notch signaling and cell differentiation. Finally, we found that HIF2-alpha 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-alpha is required for normal mouse pancreatic development. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：440 / 445

页数：6

共 17 条

[1]

Notch signalling controls pancreatic cell differentiation [J].