| First Author | Helker CSM | Year | 2019 |
| Journal | Development | Volume | 146 |
| Issue | 14 | PubMed ID | 31142539 |
| Mgi Jnum | J:295731 | Mgi Id | MGI:6453362 |
| Doi | 10.1242/dev.172569 | Citation | Helker CSM, et al. (2019) A whole organism small molecule screen identifies novel regulators of pancreatic endocrine development. Development 146(14):dev172569 |
| abstractText | An early step in pancreas development is marked by the expression of the transcription factor Pdx1 within the pancreatic endoderm, where it is required for the specification of all endocrine cell types. Subsequently, Pdx1 expression becomes restricted to the beta-cell lineage, where it plays a central role in beta-cell function. This pivotal role of Pdx1 at various stages of pancreas development makes it an attractive target to enhance pancreatic beta-cell differentiation and increase beta-cell function. In this study, we used a newly generated zebrafish reporter to screen over 8000 small molecules for modulators of pdx1 expression. We found four hit compounds and validated their efficacy at different stages of pancreas development. Notably, valproic acid treatment increased pancreatic endoderm formation, while inhibition of TGFbeta signaling led to alpha-cell to beta-cell transdifferentiation. HC toxin, another HDAC inhibitor, enhances beta-cell function in primary mouse and human islets. Thus, using a whole organism screening strategy, this study identified new pdx1 expression modulators that can be used to influence different steps in pancreas and beta-cell development. |
