Jagged1 is the major regulator of notch‐dependent cell fate in proximal airways. Issue 6 (29th April 2013)

• Record Type: Journal Article
• Authors: Zhang, Shubing; Loch, Amanda J.; Radtke, Freddy; Egan, Sean E.; Xu, Keli
• Is Part Of: Developmental dynamics. Volume 242:Issue 6(2013:Jun.)
• Page Start: 678
• Page End: 686
• Publication Date: 2013-04-29
• Subjects: Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.23965
• Languages: English
• ISSNs: 1058-8388

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p> <underline>Background:</underline> The Notch signaling pathway plays complex roles in developing lungs, including regulation of proximodistal fates, airway cell specification and differentiation. However, the specific Notch‐mediated signals involved in lung development remain unclear. <underline>Results:</underline> Here we report that <italic>Jagged1</italic> is expressed in a subset of bronchial and bronchiolar epithelial cells, where it controls proximal airway cell fate and differentiation. In agreement with previous studies involving disruption of all Notch signaling, we found that deletion of <italic>Jagged1</italic> in airway epithelium increased the number of ciliated cells at the expense of Clara cells, a phenotype associated with downregulation of <italic>Hes1</italic>. Deletion of <italic>Jagged1</italic> also led to an increased number of pulmonary neuroendocrine cells (PNEC), suggesting that Jagged1/Notch signaling inhibits PNEC cell fate. As expected, <italic>Jagged1</italic> deletion did not affect alveolar cell differentiation, although alveolar septation was impaired, likely an indirect effect of proximal airway defects. Finally, in the postnatal lung, <italic>Jagged1</italic> deletion induced mucous metaplasia, accompanied by downregulation of <italic>Hes1</italic> and <italic>Hes5</italic>. <underline>Conclusions:</underline> Our results demonstrate that Jagged1‐mediated Notch signaling regulates multiple cell fate decisions as well as differentiation in the respiratory system to coordinate lung development and to maintain a balance of airway cell types in adult life. <italic>Developmental Dynamics 242:678–686, 2013</italic>. © 2013 Wiley Periodicals, Inc.</p> </abstract>