title: Transient expression of Ngn3 in Xenopus endoderm promotes early and ectopic development of pancreatic beta and delta cells.
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 4 h 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.
authors: Laboratory of Molecular Organogenesis, Institut de recherches cliniques de Montréal, Montreal, QC, Canada.
authors: Daniel
authors: D
authors: Oropeza
authors: Marko
authors: M
authors: Horb
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D004707:Endoderm / Q000196:embryology / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000196:embryology*; D000071701:Regulatory Factor X Transcription Factors; D019864:Somatostatin-Secreting Cells / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D007328:Insulin; D000071701:Regulatory Factor X Transcription Factors; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C532313:INSM1 protein, Xenopus; C573070:NEUROG3 protein, Xenopus; C557117:Rfx6 protein, Xenopus; C097348:T-Box Domain Protein 2