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PLoS One January 1, 2013; 8 (5): e65058.

Retinoic acid-activated Ndrg1a represses Wnt/β-catenin signaling to allow Xenopus pancreas, oesophagus, stomach, and duodenum specification.

Zhang T , Guo X , Chen Y .

How cells integrate multiple patterning signals to achieve early endoderm regionalization remains largely unknown. Between gastrulation and neurulation, retinoic acid (RA) signaling is required, while Wnt/β-catenin signaling has to be repressed for the specification of the pancreas, oesophagus, stomach, and duodenum primordia in Xenopus embryos. In attempt to screen for RA regulated genes in Xenopus endoderm, we identified a direct RA target gene, N-myc downstream regulated gene 1a (ndrg1a) that showed expression early in the archenteron roof endoderm and late in the developing pancreas, oesophagus, stomach, and duodenum. Both antisense morpholino oligonucleotide mediated knockdown of ndrg1a in Xenopus laevis and the transcription activator-like effector nucleases (TALEN) mediated disruption of ndrg1 in Xenopus tropicalis demonstrate that like RA signaling, Ndrg1a is specifically required for the specification of Xenopus pancreas, oesophagus, stomach, and duodenum primordia. Immunofluorescence data suggest that RA-activated Ndrg1a suppresses Wnt/β-catenin signaling in Xenopus archenteron roof endoderm cells. Blocking Wnt/β-catenin signaling rescued Ndrg1a knockdown phenotype. Furthermore, overexpression of the putative Wnt/β-catenin target gene Atf3 phenocopied knockdown of Ndrg1a or inhibition of RA signaling, while Atf3 knockdown can rescue Ndrg1a knockdown phenotype. Lastly, the pancreas/stomach/duodenum transcription factor Pdx1 was able to rescue Atf3 overexpression or Ndrg1a knockdown phenotype. Together, we conclude that RA activated Ndrg1a represses Wnt/β-catenin signaling to allow the specification of pancreas, oesophagus, stomach, and duodenum progenitor cells in Xenopus embryos.

PubMed ID: 23741453
PMC ID: PMC3669096
Article link: PLoS One

Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: atf3 ctnnb1 ins myc ndrg1 odc1 pdx1 tff3.7
Morpholinos: atf3 MO1 ndrg1 MO1 ndrg1 MO2

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References [+] :
Afelik, Pancreatic protein disulfide isomerase (XPDIp) is an early marker for the exocrine lineage of the developing pancreas in Xenopus laevis embryos. 2003, Pubmed, Xenbase