Esophageal atresia (EA/TEF) are common congenital abnormalities of the gastrointestinal tract. The etiology of EA/TEF is not well understood. We hypothesized that EA/TEF may be the direct consequence of abnormal expression of Noggin (NOG) signaling cascade. Here we showed that, in neonates with EA/TEF, NOG was missing from the atretic esophagus, resulting in immature esophagus that contains respiratory glands, and cilia. When using mouse esophageal organoid units (EOUs) or tracheal organoid units (TOU) as a model of foregut development in vitro, NOG determined the fate of foregut progenitors by allowing expression of esophageal epithelium proteins. When NOG was present in the culture of mTOU, it altered the cell morphology of the organoid unit epithelium, allowing expression of squamous cell proteins normally found in esophagus. On the other hand, when NOG was inhibited in mEOU, the organoid epithelium began to express respiratory markers mimicking the phenotype seen in pathology samples of human EA/TEF. Moreover, human EOU derived from EA/TEF patients were small, fibrotic and lack esophageal epithelium, but when NOG was added, the EOU grew larger, healthier and express esophageal proteins. These results indicate that Noggin is a critical regulator of cell fate decisions between esophageal and pulmonary morphogenesis.
Carolina Pinzon-Guzman, Sreedhara Sangadala, Katherine M. Riera, Evgenya Y. Popova, Elizabeth Manning, Won Jae Huh, Matthew S. Alexander, Julia S. Shelton, Scott D. Boden, James R. Goldenring
Usage data is cumulative from May 2020 through July 2020.
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.