| First Author | Marty-Santos L | Year | 2016 |
| Journal | Development | Volume | 143 |
| Issue | 1 | Pages | 101-12 |
| PubMed ID | 26657766 | Mgi Jnum | J:229014 |
| Mgi Id | MGI:5750238 | Doi | 10.1242/dev.126755 |
| Citation | Marty-Santos L, et al. (2016) Pdx1 regulates pancreas tubulogenesis and E-cadherin expression. Development 143(1):101-12 |
| abstractText | Current efforts in developing treatments for diabetes focus on in vitro generation of functional beta-cells for cell replacement therapies; however, these attempts have only been partly successful because factors involved in islet formation remain incompletely understood. The embryonic pancreas, which gives rise to beta-cells, undergoes early epithelial rearrangements, including transient stratification of an initially monolayered epithelium, followed by microlumen formation and later resolution into branches. Within the epithelium, a multipotent progenitor cell (MPC) population is specified, giving rise to three important lineages: acinar, ductal and endocrine. Pdx1 is a transcription factor required for pancreas development and lineage specification; however, few Pdx1 targets that regulate pancreatogenesis have been identified. We find that pancreatic defects in Pdx1(-/-) embryos initiate at the time when the progenitor pool is specified and the epithelium should resolve into branches. Pdx1(-/-) microlumen diameters expand aberrantly, resulting in failure of epithelial tubulogenesis and ductal plexus formation. Pdx1(-/-) epithelial cell proliferation is decreased and the MPC pool is rapidly lost. We identify two conserved Pdx1 binding sites in the epithelial cadherin (E-cad, Cdh1) promoter, and show that Pdx1 directly binds and activates E-cad transcription. In addition, Pdx1 is required in vivo for maintenance of E-cad expression, actomyosin complex activity and cell shape. These findings demonstrate a novel link between regulators of epithelial architecture, specification of pancreatic cell fate and organogenesis. |
