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    Transient expression of Ngn3 in Xenopus endoderm promotes early and ectopic development of pancreatic beta and delta cells

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    Genesis-Ngn3-final.pdf (907.2Kb)
    Date
    2011-11
    Author
    Oropeza, Daniel  Concept link
    Horb, Marko E.  Concept link
    Metadata
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    Citable URI
    https://hdl.handle.net/1912/4925
    As published
    https://doi.org/10.1002/dvg.20828
    Keyword
     Diabetes; Reprogramming; Endoderm progenitor; Microarray; Endocrine; Transcription factor; Hormone inducible 
    Abstract
    Promoting ectopic development of pancreatic beta cells from other cell types is one of the strategies being pursued for the treatment of diabetes. To achieve this, a detailed outline of the molecular lineage that operates in pancreatic progenitor cells to generate beta cells over other endocrine cell types is necessary. Here, we demonstrate that early transient expression of the endocrine progenitor bHLH protein Neurogenin 3 (Ngn3) favors the promotion of pancreatic beta and delta cell fates over an alpha cell fate, while later transient expression promotes ectopic development of all three endocrine cell fates. We found that short-term activation of Ngn3 in Xenopus laevis endoderm just after gastrulation was sufficient to promote both early and ectopic development of beta and delta cells. By examining gene expression changes four hours after Ngn3 activation we identified several new downstream targets of Ngn3. We show that several of these are required for the promotion of ectopic beta cells by Ngn3 as well as for normal beta cell development. These results provide new detail regarding the Ngn3 transcriptional network operating in endocrine progenitor cells to specify a beta cell phenotype and should help define new approaches to promote ectopic development of beta cells for diabetes therapy.
    Description
    Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in genesis 50 (2012): 271-285, doi:10.1002/dvg.20828.
    Collections
    • Bell Center Publications
    Suggested Citation
    Preprint: Oropeza, Daniel, Horb, Marko E., "Transient expression of Ngn3 in Xenopus endoderm promotes early and ectopic development of pancreatic beta and delta cells", 2011-11, https://doi.org/10.1002/dvg.20828, https://hdl.handle.net/1912/4925
     

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