Hippo Signaling Regulates Pancreas Development through Inactivation of Yap
Hippo Signaling Regulates Pancreas Development through Inactivation of Yap
The mammalian pancreas is required for normal metabolism, with defects in this vital organ commonly observed in cancer and diabetes. Development must therefore be tightly controlled in order to produce a pancreas of correct size, cell type composition, and physiologic function. Through negative regulation of Yap-dependent proliferation, the Hippo kinase cascade is a critical regulator of organ growth. To investigate the role of Hippo signaling in pancreas biology, we deleted Hippo pathway components in the developing mouse pancreas. Unexpectedly, the pancreas from Hippo-deficient offspring was reduced in size, with defects evident throughout the organ. Increases in the dephosphorylated nuclear form of Yap are apparent throughout the exocrine compartment and correlate with increases in levels of cell proliferation. However, the mutant exocrine tissue displays extensive disorganization leading to pancreatitis-like autodigestion. Interestingly, our results suggest that Hippo signaling does not directly regulate the pancreas endocrine compartment as Yap expression is lost following endocrine specification through a Hippo-independent mechanism. Altogether, our results demonstrate that Hippo signaling plays a crucial role in pancreas development and provide novel routes to a better understanding of pathological conditions that affect this organ.
- University of Nebraska Medical Center United States
- The University of Texas MD Anderson Cancer Center United States
Male, Mice, Knockout, Hepatocyte Growth Factor, Protein Stability, Intracellular Signaling Peptides and Proteins, Gene Expression Regulation, Developmental, Cell Cycle Proteins, Protein Serine-Threonine Kinases, Phosphoproteins, Immunohistochemistry, Serine-Threonine Kinase 3, Mice, Pregnancy, Proto-Oncogene Proteins, Animals, Female, Pancreas, Adaptor Proteins, Signal Transducing, Cell Proliferation, Signal Transduction
Male, Mice, Knockout, Hepatocyte Growth Factor, Protein Stability, Intracellular Signaling Peptides and Proteins, Gene Expression Regulation, Developmental, Cell Cycle Proteins, Protein Serine-Threonine Kinases, Phosphoproteins, Immunohistochemistry, Serine-Threonine Kinase 3, Mice, Pregnancy, Proto-Oncogene Proteins, Animals, Female, Pancreas, Adaptor Proteins, Signal Transducing, Cell Proliferation, Signal Transduction
105 Research products, page 1 of 11
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
- 4
- 5
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).113 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
