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Genesis 2012 Mar 01;503:271-85. doi: 10.1002/dvg.20828.
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Transient expression of Ngn3 in Xenopus endoderm promotes early and ectopic development of pancreatic beta and delta cells.

Oropeza D , Horb M .

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.

PubMed ID: 22121111
PMC ID: PMC3294191
Article link: Genesis
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: abcc8 aif1l ankrd37 arl5b asb5 atoh7 bmp7.1 btg5.2 cbfa2t2 cbfa2t3 ccnb1 cela1.2 cela1.6 cer1 chn2 chst10 ctse dbn1 dbndd1 dlc dlc1 dll1 egln3 elavl3 fgf13 foxa4 foxf1 frzb gadd45g gcg gmnn gramd2b hba3 hes3 hes5 hes5.10 hes5.3 hes5.5 hes5.7 hey1 hhex hoxd1 igf2 ins insm1 irf6 kcnk5 mcoln2 mespb mospd1 mxi1 ndrg4 neurod4 neurog1 neurog3 nudt22 pax4 pdia2 pdk4 pgam1 pik3ip1 pou4f1 pou5f3.2 ppm1k ppp1r14a prag1 prss3 ptgs2 rfesd rflnb rfx6 rgs1 ripply2.1 runx1t1 sat1 slc16a3 slc3a2 slc7a8 sst.1 stmn3 tbx2 tob1 tsc22d3 tspan8 twist1 twsg1 unc119b unc93a.2 ventx1 zfand2a
GO keywords: type B pancreatic cell development
Morpholinos: cbfa2t2 MO1 cbfa2t3 MO1 insm1 MO1 insm1 MO2 rfx6 MO1 rfx6 MO2 runx1t1 MO1 tbx2 MO1

Disease Ontology terms: diabetes mellitus
GEO Series: GSE29017: NCBI
Phenotypes: Xla Wt + Hsa.neurog3-GR + DEX (Fig 3f) [+]

Article Images: [+] show captions
References [+] :
Aaker, Feedback regulation of NEUROG2 activity by MTGR1 is required for progression of neurogenesis. 2009, Pubmed