| First Author | Jimenez-Caliani AJ | Year | 2017 |
| Journal | Cell Rep | Volume | 20 |
| Issue | 6 | Pages | 1295-1306 |
| PubMed ID | 28793255 | Mgi Jnum | J:255472 |
| Mgi Id | MGI:6107747 | Doi | 10.1016/j.celrep.2017.07.035 |
| Citation | Jimenez-Caliani AJ, et al. (2017) alphaE-Catenin Is a Positive Regulator of Pancreatic Islet Cell Lineage Differentiation. Cell Rep 20(6):1295-1306 |
| abstractText | The development and function of epithelia depend on the establishment and maintenance of cell-cell adhesion and intercellular junctions, which operate as mechanosensor hubs for the transduction of biochemical signals regulating cell proliferation, differentiation, survival, and regeneration. Here, we show that alphaE-catenin, a key component of adherens junctions, functions as a positive regulator of pancreatic islet cell lineage differentiation by repressing the sonic hedgehog pathway (SHH). Thus, deletion of alphaE-catenin in multipotent pancreatic progenitors resulted in (1) loss of adherens junctions, (2) constitutive activation of SHH, (3) decrease in islet cell lineage differentiation, and (4) accumulation of immature Sox9(+) progenitors. Pharmacological blockade of SHH signaling in pancreatic organ cultures and in vivo rescued this defect, allowing alphaE-catenin-null Sox9(+) pancreatic progenitors to differentiate into endocrine cells. The results uncover crucial functions of alphaE-catenin in pancreatic islet development and harbor significant implications for the design of beta cell replacement and regeneration therapies in diabetes. |
