Noggin regulates foregut progenitor cell programming, and misexpression leads to esophageal atresia

J Clin Invest. 2020 Aug 3;130(8):4396-4410. doi: 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: Development; Embryonic development; Human stem cells; Surgery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation*
  • Cell Line
  • Esophageal Atresia / embryology*
  • Esophageal Atresia / genetics
  • Esophageal Atresia / pathology
  • Gene Expression Regulation, Developmental*
  • Humans
  • Mice
  • Models, Biological*
  • Organoids / embryology
  • Organoids / pathology
  • Stem Cells / metabolism*
  • Stem Cells / pathology

Substances

  • Carrier Proteins
  • noggin protein