1. Noggin regulates foregut progenitor cell programming, and misexpression leads to esophageal atresia.
- Author
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Pinzon-Guzman C, Sangadala S, Riera KM, Popova EY, Manning E, Huh WJ, Alexander MS, Shelton JS, Boden SD, and Goldenring JR
- Subjects
- Animals, Carrier Proteins genetics, Cell Line, Esophageal Atresia genetics, Esophageal Atresia pathology, Humans, Mice, Organoids embryology, Organoids pathology, Stem Cells pathology, Carrier Proteins metabolism, Cell Differentiation, Esophageal Atresia embryology, Gene Expression Regulation, Developmental, Models, Biological, Stem Cells metabolism
- 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.
- Published
- 2020
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