Noggin regulates foregut progenitor cell programming, and misexpression leads to esophageal atresia
- 2 August 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 130 (8), 4396-4410
- https://doi.org/10.1172/JCI123597
Abstract
Esophageal atresia (EA/TEF) is a common congenital abnormality present in 1 of 4000 births. Here we show that atretic esophagi lack Noggin (NOG) expression, resulting in immature esophagus that contains respiratory glands. Moreover, when using mouse esophageal organoid units (EOUs) or tracheal organoid units (TOUs) as a model of foregut development and differentiation in vitro, NOG determines whether foregut progenitors differentiate toward esophageal or tracheal epithelium. These results indicate that NOG is a critical regulator of cell fate decisions between esophageal and pulmonary morphogenesis, and its lack of expression results in EA/TEF.Keywords
Funding Information
- Department of Veterans Affairs Merit Review (Award (I01 BX000930))
- DOD (CA160479)
- NIH (RO1 DK071590)
- The Helen and Nicholas Abumrad Research Fund (NA)
- NIH (T32 CA106183)
- Vanderbilt (VICTR (VR15139.1))
- NIH (R21TR001751)
- Emory (Emory Orthopaedics Seed Grant)
- Vanderbilt (Vanderbilt Digestive Disease Center, (P30 DK058404))
This publication has 23 references indexed in Scilit:
- VATER/VACTERL Association: Evidence for the Role of Genetic FactorsMolecular Syndromology, 2012
- Oesophageal atresia: prevalence, prenatal diagnosis and associated anomalies in 23 European regionsArchives of Disease in Childhood, 2012
- Mapping and analysis of chromatin state dynamics in nine human cell typesNature, 2011
- BMP signaling in the development of the mouse esophagus and forestomachDevelopment, 2010
- Discovery and characterization of chromatin states for systematic annotation of the human genomeNature Biotechnology, 2010
- Virtual screening and selection of drug-like compounds to block noggin interaction with bone morphogenetic proteinsJournal of Molecular Graphics and Modelling, 2010
- Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endodermDevelopment, 2007
- Aberrant Bmp signaling and notochord delamination in the pathogenesis of esophageal atresiaDevelopmental Dynamics, 2007
- Morphogenesis of the trachea and esophagus: current players and new roles for noggin and BmpsDifferentiation, 2006
- Smad transcription factorsGenes & Development, 2005