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XB-ART-44499
Genesis. March 1, 2012; 50 (3): 271-85.

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.

PubMed ID: 22121111
PMC ID: PMC3294191
Article link: Genesis.
Grant support: DK077197 NIDDK NIH HHS , R01 DK077197 NIDDK NIH HHS , R01 DK077197-05 NIDDK NIH HHS , P40 OD010997 NIH HHS , R01 DK077197 NIDDK NIH HHS , R01 DK077197-05 NIDDK NIH HHS , DK077197 NIDDK NIH HHS

Genes referenced: abcc8 aif1l ankrd37 arl5b asb5 atoh7 bmp7.1 btg5 cbfa2t2 cbfa2t3 ccnb1 cer1 chn1 chst10 ctse dbn1 dbndd1 dlc dlc1 dll1 egln3 elavl3 esr10 fgf13 foxa4 foxf1 frzb gadd45g gcg gmnn gramd2b hba3 hes3.1 hes3.3 hes5.1 hes9.1 hey1 hhex hoxd1 igf2 ins insm1 irf6 kcnk5 loc100135144 mcoln2 mespb mospd1 mxi1 ndrg4 neurod4 neurog1 neurog3 nudt22 pax4 pdia2 pdk4 pgam1 pik3ip1 pou4f1 pou5f3.2 ppm1k ppp1r14a prag1 ptgs2 rfesd rflnb rfx6 rgs1 ripply2.1 runx1t1 sat1 slc16a3 slc3a2 slc7a8 sst stmn3 tbx2 tob1 tsc22d3 tspan8 twist1 twsg1 unc119b unc93a ventx1.1 zfand2a

Morpholinos referenced: cbfa2t2 MO1 cbfa2t3 MO1 insm1 MO1 insm1 MO2 rfx6 MO1 rfx6 MO2 runx1t1 MO1 tbx2 MO1

References:
Aaker, 2009, Pubmed[+]


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