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Retinoic Acid-Activated Ndrg1a Represses Wnt/β-catenin Signaling to Allow Xenopus Pancreas, Oesophagus, Stomach, and Duodenum Specification

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, stom...

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Autores principales: Zhang, Tiejun, Guo, Xiaogang, Chen, Yonglong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669096/
https://www.ncbi.nlm.nih.gov/pubmed/23741453
http://dx.doi.org/10.1371/journal.pone.0065058
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author Zhang, Tiejun
Guo, Xiaogang
Chen, Yonglong
author_facet Zhang, Tiejun
Guo, Xiaogang
Chen, Yonglong
author_sort Zhang, Tiejun
collection PubMed
description 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.
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spelling pubmed-36690962013-06-05 Retinoic Acid-Activated Ndrg1a Represses Wnt/β-catenin Signaling to Allow Xenopus Pancreas, Oesophagus, Stomach, and Duodenum Specification Zhang, Tiejun Guo, Xiaogang Chen, Yonglong PLoS One Research Article 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. Public Library of Science 2013-05-31 /pmc/articles/PMC3669096/ /pubmed/23741453 http://dx.doi.org/10.1371/journal.pone.0065058 Text en © 2013 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhang, Tiejun
Guo, Xiaogang
Chen, Yonglong
Retinoic Acid-Activated Ndrg1a Represses Wnt/β-catenin Signaling to Allow Xenopus Pancreas, Oesophagus, Stomach, and Duodenum Specification
title Retinoic Acid-Activated Ndrg1a Represses Wnt/β-catenin Signaling to Allow Xenopus Pancreas, Oesophagus, Stomach, and Duodenum Specification
title_full Retinoic Acid-Activated Ndrg1a Represses Wnt/β-catenin Signaling to Allow Xenopus Pancreas, Oesophagus, Stomach, and Duodenum Specification
title_fullStr Retinoic Acid-Activated Ndrg1a Represses Wnt/β-catenin Signaling to Allow Xenopus Pancreas, Oesophagus, Stomach, and Duodenum Specification
title_full_unstemmed Retinoic Acid-Activated Ndrg1a Represses Wnt/β-catenin Signaling to Allow Xenopus Pancreas, Oesophagus, Stomach, and Duodenum Specification
title_short Retinoic Acid-Activated Ndrg1a Represses Wnt/β-catenin Signaling to Allow Xenopus Pancreas, Oesophagus, Stomach, and Duodenum Specification
title_sort retinoic acid-activated ndrg1a represses wnt/β-catenin signaling to allow xenopus pancreas, oesophagus, stomach, and duodenum specification
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669096/
https://www.ncbi.nlm.nih.gov/pubmed/23741453
http://dx.doi.org/10.1371/journal.pone.0065058
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