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 disruption of RA signaling within the NEUROG3-expressing endocrine progenitor population impairs mouse β cell differentiation and induces ectopic expression of critical δ cell genes, including Somatostatin. In addition, inhibition of the RA pathway in hESC-derived pancreatic progenitors downstream of NEUROG3 induction impairs INSULIN expression. We further determine that RA-regulation of endocrine cell differentiation is mediated 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.
Retinoic acid signaling within pancreatic endocrine progenitors regulates mouse and human β cell specification
Lead contact
Currently Viewing Accepted Manuscript - Newer Version Available
David S. Lorberbaum, Siddharth Kishore, Carolina Rosselot, Dylan Sarbaugh, Elliott P. Brooks, Eloise Aragon, Shouhong Xuan, Olivier Simon, Debashis Ghosh, Cathy Mendelsohn, Paul Gadue, Lori Sussel; Retinoic acid signaling within pancreatic endocrine progenitors regulates mouse and human β cell specification. Development 2020; dev.189977. doi: https://doi.org/10.1242/dev.189977
Download citation file:
Advertisement
Call for papers: Uncovering Developmental Diversity
Development invites you to submit your latest research to our upcoming special issue: Uncovering Developmental Diversity. This issue will be coordinated by our academic Editor Cassandra Extavour (Harvard University, USA) alongside two Guest Editors: Liam Dolan (Gregor Mendel Institute of Molecular Plant Biology, Austria) and Karen Sears (University of California Los Angeles, USA).
Choose Development in 2024
In this Editorial, Development Editor-in-Chief James Briscoe and Executive Editor Katherine Brown explain how you support your community by publishing in Development and how the journal champions serious science, community connections and progressive publishing.
Journal Meeting: From Stem Cells to Human Development
Register now for the 2024 Development Journal Meeting From Stem Cells to Human Development. Early-bird registration deadline: 3 May. Abstract submission deadline: 21 June.
Pluripotency of a founding field: rebranding developmental biology
This collaborative Perspective, the result of a workshop held in 2023, proposes a set of community actions to increase the visibility of the developmental biology field. The authors make recommendations for new funding streams, frameworks for collaborations and mechanisms by which members of the community can promote themselves and their research.
Read & Publish Open Access publishing: what authors say
We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.