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

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.

SUBMITTER: Pinzon-Guzman C

PROVIDER: S-EPMC7410075 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Pinzon-Guzman Carolina C Sangadala Sreedhara S Riera Katherine M KM Popova Evgenya Y EY Manning Elizabeth E Huh Won Jae WJ Alexander Matthew S MS Shelton Julia S JS Boden Scott D SD Goldenring James R JR

The Journal of clinical investigation 20200801 8

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 indica ...[more]

PMID: 32427591

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Project description:BackgroundA communicating bronchopulmonary foregut malformation (CBPFM) group IB is very rare congenital malformation. Group IB is associated with tracheoesophageal fistula and esophageal atresia (TEF-EA) and a portion of one lung arisen from the esophagus (Gerle et al. in N Engl J Med. 278:1413-1419, 1968). The coexistence of TEF-EA and dextrocardia is also a rare and challenging setting for repair of TEF-EA. Therefore, the thoracoscopic surgery for TEF-EA require the technical devise because of the small operative space. We herein report a rare case of CBPFM group IB with intralobar sequestration of lung and a successful performing of thoracoscopic surgery for EA with dextrocardia in VACTERL association.Case presentationA 2.2-kg term male neonate was born with an anal atresia, coarctation of the aorta, TEF-EA, renal anomalies, radial hemimelia, limb abnormalities (VACTERL association) and hypoplasia of the right lung with dextrocardia. The patient developed respiratory distress after admission. A two-stage operation for the TEF-EA was planned because of multiple anomalies and cardiac condition. In the neonatal period, esophageal banding at the gastroesophageal junction and gastrostomy were performed to establish enteral nutrition. After gaining body weight and achieving a stable cardiac condition, thoracoscopic surgery for TEF-EA was performed. The thoracoscopic findings revealed a small working space due to dextrocardia. To obtain a sufficient working space and to perform secure esophageal anastomosis, an additional 3-mm assistant port was inserted. To close the upper and lower esophagus, anchoring sutures of the esophagus were placed and were pulled to suspend the anastomotic site. Esophageal anastomosis was successfully performed. An esophagogram after TEF-EA surgery showed the connection between the lower esophagus and right lower lung. The definitive diagnosis was CBPFM group IB with intralobar sequestration. The thoracoscopic surgery was performed again for establishing oral intake. After transection of the bronchoesophageal fistula, the patient could perform oral feeding without pneumonia or respiratory distress.ConclusionsCBPFM type IB with intralobar sequestration is a rare condition. CBPFM type IB should be considered for a patients with respiratory symptom after radical operation for TEF-EA. In the present case, suspending the anastomotic site was effective and useful in thoracoscopic surgery for a TEF-EA patient with dextrocardia.

Project description:BackgroundChildren with long-gap esophageal atresia (LGEA) risk living with aerodigestive morbidity and mental health difficulties. No previous study has investigated their experiences of schooling, despite the importance of schools in children's development, learning and social relationships. We aimed to describe experiences of schooling in children with LGEA in Sweden in comparison with children with EA who had primary anastomosis.MethodChildren with LGEA aged 3-17 were recruited nationwide in Sweden. One parent completed a survey on their child's school-based supports (according to definitions from the Swedish National Agency for Education), school absence, school satisfaction, school functioning (PedsQL 4.0), mental health (Strength and Difficulties Questionnaire) and current symptomatology. School data were compared between 26 children with LGEA to that from 95 children with EA who had PA, a hypothesized milder affected group. Mental health level was determined using validated norms; abnormal ≥ 90 percentile. Data were analyzed using descriptives, correlation and Mann-Whitney-U test. Significance level was p < 0.05.ResultsFormal school-based support was reported in 17 (65.4%) children with LGEA and concerned support with nutritional intake (60%), education (50%) and medical/special health needs (35%). The prevalence of school-based support was significantly higher compared to children with PA overall (36.8%, p = 0.013) and regarding nutritional intake support (20%, p < 0.001). In children with LGEA, school-based support was related to low birth weight (p = 0.036), young child age (p = 0.014), height ≤ -2SD for age/sex (p = 0.024) and an increased number of aerodigestive symptoms (p < 0.05). All children with LGEA who had abnormal mental health scores had school-based support, except for one child. Nine children with LGEA (36%) had school absence ≥ 1times/month the past year, more frequently because of colds/airway infections (p = 0.045) and GI-specific problems compared to PA (p = 0.003). School functioning scores were not significantly different from children with PA (p = 0.34) but correlated negatively with school-based support (< 0.001) and school absence (p = 0.002). One parent out of 26 reported their child's school satisfaction as "not good".ConclusionsChildren with LGEA commonly receive school-based support, reflecting multifaceted daily needs and disease severity. School absence is frequent and related to poorer school functioning. Future research focusing on academic achievement in children with EA is needed.

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

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

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