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Notch Signaling Regulates Bile Duct Morphogenesis in Mice
BACKGROUND: Alagille syndrome is a developmental disorder caused predominantly by mutations in the Jagged1 (JAG1) gene, which encodes a ligand for Notch family receptors. A characteristic feature of Alagille syndrome is intrahepatic bile duct paucity. We described previously that mice doubly heteroz...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266994/ https://www.ncbi.nlm.nih.gov/pubmed/18365007 http://dx.doi.org/10.1371/journal.pone.0001851 |
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author | Lozier, Julie McCright, Brent Gridley, Thomas |
author_facet | Lozier, Julie McCright, Brent Gridley, Thomas |
author_sort | Lozier, Julie |
collection | PubMed |
description | BACKGROUND: Alagille syndrome is a developmental disorder caused predominantly by mutations in the Jagged1 (JAG1) gene, which encodes a ligand for Notch family receptors. A characteristic feature of Alagille syndrome is intrahepatic bile duct paucity. We described previously that mice doubly heterozygous for Jag1 and Notch2 mutations are an excellent model for Alagille syndrome. However, our previous study did not establish whether bile duct paucity in Jag1/Notch2 double heterozygous mice resulted from impaired differentiation of bile duct precursor cells, or from defects in bile duct morphogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Here we characterize embryonic biliary tract formation in our previously described Jag1/Notch2 double heterozygous Alagille syndrome model, and describe another mouse model of bile duct paucity resulting from liver-specific deletion of the Notch2 gene. CONCLUSIONS/SIGNIFICANCE: Our data support a model in which bile duct paucity in Notch pathway loss of function mutant mice results from defects in bile duct morphogenesis rather than cell fate specification. |
format | Text |
id | pubmed-2266994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-22669942008-03-26 Notch Signaling Regulates Bile Duct Morphogenesis in Mice Lozier, Julie McCright, Brent Gridley, Thomas PLoS One Research Article BACKGROUND: Alagille syndrome is a developmental disorder caused predominantly by mutations in the Jagged1 (JAG1) gene, which encodes a ligand for Notch family receptors. A characteristic feature of Alagille syndrome is intrahepatic bile duct paucity. We described previously that mice doubly heterozygous for Jag1 and Notch2 mutations are an excellent model for Alagille syndrome. However, our previous study did not establish whether bile duct paucity in Jag1/Notch2 double heterozygous mice resulted from impaired differentiation of bile duct precursor cells, or from defects in bile duct morphogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Here we characterize embryonic biliary tract formation in our previously described Jag1/Notch2 double heterozygous Alagille syndrome model, and describe another mouse model of bile duct paucity resulting from liver-specific deletion of the Notch2 gene. CONCLUSIONS/SIGNIFICANCE: Our data support a model in which bile duct paucity in Notch pathway loss of function mutant mice results from defects in bile duct morphogenesis rather than cell fate specification. Public Library of Science 2008-03-26 /pmc/articles/PMC2266994/ /pubmed/18365007 http://dx.doi.org/10.1371/journal.pone.0001851 Text en Lozier 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 Lozier, Julie McCright, Brent Gridley, Thomas Notch Signaling Regulates Bile Duct Morphogenesis in Mice |
title | Notch Signaling Regulates Bile Duct Morphogenesis in Mice |
title_full | Notch Signaling Regulates Bile Duct Morphogenesis in Mice |
title_fullStr | Notch Signaling Regulates Bile Duct Morphogenesis in Mice |
title_full_unstemmed | Notch Signaling Regulates Bile Duct Morphogenesis in Mice |
title_short | Notch Signaling Regulates Bile Duct Morphogenesis in Mice |
title_sort | notch signaling regulates bile duct morphogenesis in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2266994/ https://www.ncbi.nlm.nih.gov/pubmed/18365007 http://dx.doi.org/10.1371/journal.pone.0001851 |
work_keys_str_mv | AT lozierjulie notchsignalingregulatesbileductmorphogenesisinmice AT mccrightbrent notchsignalingregulatesbileductmorphogenesisinmice AT gridleythomas notchsignalingregulatesbileductmorphogenesisinmice |