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Publication : Retinoic acid signaling within pancreatic endocrine progenitors regulates mouse and human β cell specification.

First Author  Lorberbaum DS Year  2020
Journal  Development Volume  147
Issue  12 PubMed ID  32467243
Mgi Jnum  J:290417 Mgi Id  MGI:6442235
Doi  10.1242/dev.189977 Citation  Lorberbaum DS, et al. (2020) Retinoic acid signaling within pancreatic endocrine progenitors regulates mouse and human beta cell specification. Development 147(12):dev189977
abstractText  Retinoic acid (RA) signaling is essential for multiple developmental processes, including appropriate pancreas formation from the foregut endoderm. RA is also required to generate pancreatic progenitors from human pluripotent stem cells. However, the role of RA signaling during endocrine specification has not been fully explored. In this study, we demonstrate that the disruption of RA signaling within the NEUROG3-expressing endocrine progenitor population impairs mouse beta cell differentiation and induces ectopic expression of crucial delta cell genes, including somatostatin. In addition, the inhibition of the RA pathway in hESC-derived pancreatic progenitors downstream of NEUROG3 induction impairs insulin expression. We further determine that RA-mediated regulation of endocrine cell differentiation occurs through Wnt pathway components. Together, these data demonstrate the importance of RA signaling in endocrine specification and identify conserved mechanisms by which RA signaling directs pancreatic endocrine cell fate.
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