| First Author | Baumgartner BK | Year | 2014 |
| Journal | Dev Biol | Volume | 391 |
| Issue | 1 | Pages | 89-98 |
| PubMed ID | 24721715 | Mgi Jnum | J:213751 |
| Mgi Id | MGI:5585702 | Doi | 10.1016/j.ydbio.2014.03.019 |
| Citation | Baumgartner BK, et al. (2014) Distinct requirements for beta-catenin in pancreatic epithelial growth and patterning. Dev Biol 391(1):89-98 |
| abstractText | Pancreatic exocrine and endocrine lineages arise from multipotent pancreatic progenitor cells (MPCs). Exploiting the mechanisms that govern expansion and differentiation of these cells could enhance efforts to generate beta-cells from stem cells. Although our prior work indicates that the canonical Wnt signaling component beta-catenin is required qualitatively for exocrine acinar but not endocrine development, precisely how this requirement plays out at the level of MPCs and their lineage-restricted progeny is unknown. In addition, the contribution of beta-catenin function to beta-cell development remains controversial. To resolve the potential roles of beta-catenin in development of MPCs and beta-cells, we generated pancreas- and pre-endocrine-specific beta-catenin knockout mice. Pancreas-specific loss of beta-catenin produced not only a dramatic reduction in acinar cell numbers, but also a significant reduction in beta-cell mass. The loss of beta-cells is due not to a defect in the differentiation of endocrine precursors, but instead correlates with an early and specific loss of MPCs. In turn, this reflects a novel role for beta-catenin in maintaining proximal-distal patterning of the early epithelium, such that distal MPCs resort to a proximal, endocrine-competent "trunk" fate when beta-catenin is deleted. Moreover, beta-catenin maintains proximal-distal patterning, in part, by inhibiting Notch signaling. Subsequently, beta-catenin is required for proliferation of both distal and proximal cells, driving overall organ growth. In distinguishing two distinct roles for beta-catenin along the route of beta-cell development, we suggest that temporally appropriate positive and negative manipulation of this molecule could enhance expansion and differentiation of stem cell-derived MPCs. |
