Jagged1 is the major regulator of notch‐dependent cell fate in proximal airways
ABSTRACT Background: 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. Results: Here we report that...
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Veröffentlicht in: | Developmental dynamics 2013-06, Vol.242 (6), p.678-686 |
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description | ABSTRACT
Background: 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. Results: Here we report that Jagged1 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 Jagged1 in airway epithelium increased the number of ciliated cells at the expense of Clara cells, a phenotype associated with downregulation of Hes1. Deletion of Jagged1 also led to an increased number of pulmonary neuroendocrine cells (PNEC), suggesting that Jagged1/Notch signaling inhibits PNEC cell fate. As expected, Jagged1 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, Jagged1 deletion induced mucous metaplasia, accompanied by downregulation of Hes1 and Hes5. Conclusions: 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. Developmental Dynamics 242:678–686, 2013. © 2013 Wiley Periodicals, Inc.
Key Findings
Jagged1 regulates airway cell fate decision in the developing lung
Jagged1 prevents mucous metaplasia in the postnatal lung
Jagged1 influences alveologenesis |
doi_str_mv | 10.1002/dvdy.23965 |
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Background: 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. Results: Here we report that Jagged1 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 Jagged1 in airway epithelium increased the number of ciliated cells at the expense of Clara cells, a phenotype associated with downregulation of Hes1. Deletion of Jagged1 also led to an increased number of pulmonary neuroendocrine cells (PNEC), suggesting that Jagged1/Notch signaling inhibits PNEC cell fate. As expected, Jagged1 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, Jagged1 deletion induced mucous metaplasia, accompanied by downregulation of Hes1 and Hes5. Conclusions: 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. Developmental Dynamics 242:678–686, 2013. © 2013 Wiley Periodicals, Inc.
Key Findings
Jagged1 regulates airway cell fate decision in the developing lung
Jagged1 prevents mucous metaplasia in the postnatal lung
Jagged1 influences alveologenesis</description><identifier>ISSN: 1058-8388</identifier><identifier>EISSN: 1097-0177</identifier><identifier>DOI: 10.1002/dvdy.23965</identifier><identifier>PMID: 23526493</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>airway cell fate ; Animals ; Calcium-Binding Proteins - genetics ; Calcium-Binding Proteins - physiology ; Cell Differentiation ; Cell Lineage ; Epithelial Cells - metabolism ; Gene Expression Regulation, Developmental ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins - genetics ; Intercellular Signaling Peptides and Proteins - physiology ; Jagged-1 Protein ; Jagged1 ; lung ; Lung - embryology ; Lung - metabolism ; Membrane Proteins - genetics ; Membrane Proteins - physiology ; Mice ; Mice, Transgenic ; mucous metaplasia ; Neuroendocrine Cells - metabolism ; Notch ; Phenotype ; Receptors, Notch - metabolism ; Serrate-Jagged Proteins ; Signal Transduction ; Time Factors</subject><ispartof>Developmental dynamics, 2013-06, Vol.242 (6), p.678-686</ispartof><rights>Copyright © 2013 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4595-9094d79c755be2d2ccad2885476e207c4074bd54293efa317bb3331c2161864f3</citedby><cites>FETCH-LOGICAL-c4595-9094d79c755be2d2ccad2885476e207c4074bd54293efa317bb3331c2161864f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fdvdy.23965$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fdvdy.23965$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,782,786,1419,1435,27931,27932,45581,45582,46416,46840</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23526493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Shubing</creatorcontrib><creatorcontrib>Loch, Amanda J.</creatorcontrib><creatorcontrib>Radtke, Freddy</creatorcontrib><creatorcontrib>Egan, Sean E.</creatorcontrib><creatorcontrib>Xu, Keli</creatorcontrib><title>Jagged1 is the major regulator of notch‐dependent cell fate in proximal airways</title><title>Developmental dynamics</title><addtitle>Dev Dyn</addtitle><description>ABSTRACT
Background: 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. Results: Here we report that Jagged1 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 Jagged1 in airway epithelium increased the number of ciliated cells at the expense of Clara cells, a phenotype associated with downregulation of Hes1. Deletion of Jagged1 also led to an increased number of pulmonary neuroendocrine cells (PNEC), suggesting that Jagged1/Notch signaling inhibits PNEC cell fate. As expected, Jagged1 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, Jagged1 deletion induced mucous metaplasia, accompanied by downregulation of Hes1 and Hes5. Conclusions: 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. Developmental Dynamics 242:678–686, 2013. © 2013 Wiley Periodicals, Inc.
Key Findings
Jagged1 regulates airway cell fate decision in the developing lung
Jagged1 prevents mucous metaplasia in the postnatal lung
Jagged1 influences alveologenesis</description><subject>airway cell fate</subject><subject>Animals</subject><subject>Calcium-Binding Proteins - genetics</subject><subject>Calcium-Binding Proteins - physiology</subject><subject>Cell Differentiation</subject><subject>Cell Lineage</subject><subject>Epithelial Cells - metabolism</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Immunohistochemistry</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Intercellular Signaling Peptides and Proteins - physiology</subject><subject>Jagged-1 Protein</subject><subject>Jagged1</subject><subject>lung</subject><subject>Lung - embryology</subject><subject>Lung - metabolism</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - physiology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>mucous metaplasia</subject><subject>Neuroendocrine Cells - metabolism</subject><subject>Notch</subject><subject>Phenotype</subject><subject>Receptors, Notch - metabolism</subject><subject>Serrate-Jagged Proteins</subject><subject>Signal Transduction</subject><subject>Time Factors</subject><issn>1058-8388</issn><issn>1097-0177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKxDAUhoMo3jc-gATciNAx16ZdyoxXBBFUcFXS5HSmQ6cdk1adnY_gM_okZi66cOHq_IuPj__8CB1Q0qOEsFP7amc9xtNYrqFtSlIVEarU-jzLJEp4kmyhHe_HhJAkFnQTbTEuWSxSvo3ub_RwCJbi0uN2BHiix43DDoZdpduQmgLXTWtGXx-fFqZQW6hbbKCqcKFbwGWNp655Lye6wrp0b3rm99BGoSsP-6u7ix4vzh_6V9Ht3eV1_-w2MkKmMkpJKqxKjZIyB2aZMdqyJJFCxcCIMoIokVspWMqh0JyqPOecU8NoTMMXBd9Fx0tvKPDSgW-zSennzXQNTeczyiUXKuExC-jRH3TcdK4O7RYUoYTFNFAnS8q4xnsHRTZ14TE3yyjJ5kNn86GzxdABPlwpu3wC9hf9WTYAdAm8lRXM_lFlg6fB81L6DdSLh6k</recordid><startdate>201306</startdate><enddate>201306</enddate><creator>Zhang, Shubing</creator><creator>Loch, Amanda J.</creator><creator>Radtke, Freddy</creator><creator>Egan, Sean E.</creator><creator>Xu, Keli</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SS</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>JQ2</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201306</creationdate><title>Jagged1 is the major regulator of notch‐dependent cell fate in proximal airways</title><author>Zhang, Shubing ; Loch, Amanda J. ; Radtke, Freddy ; Egan, Sean E. ; Xu, Keli</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4595-9094d79c755be2d2ccad2885476e207c4074bd54293efa317bb3331c2161864f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>airway cell fate</topic><topic>Animals</topic><topic>Calcium-Binding Proteins - genetics</topic><topic>Calcium-Binding Proteins - physiology</topic><topic>Cell Differentiation</topic><topic>Cell Lineage</topic><topic>Epithelial Cells - metabolism</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Immunohistochemistry</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Intercellular Signaling Peptides and Proteins - physiology</topic><topic>Jagged-1 Protein</topic><topic>Jagged1</topic><topic>lung</topic><topic>Lung - embryology</topic><topic>Lung - metabolism</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - physiology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>mucous metaplasia</topic><topic>Neuroendocrine Cells - metabolism</topic><topic>Notch</topic><topic>Phenotype</topic><topic>Receptors, Notch - metabolism</topic><topic>Serrate-Jagged Proteins</topic><topic>Signal Transduction</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Shubing</creatorcontrib><creatorcontrib>Loch, Amanda J.</creatorcontrib><creatorcontrib>Radtke, Freddy</creatorcontrib><creatorcontrib>Egan, Sean E.</creatorcontrib><creatorcontrib>Xu, Keli</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Developmental dynamics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Shubing</au><au>Loch, Amanda J.</au><au>Radtke, Freddy</au><au>Egan, Sean E.</au><au>Xu, Keli</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Jagged1 is the major regulator of notch‐dependent cell fate in proximal airways</atitle><jtitle>Developmental dynamics</jtitle><addtitle>Dev Dyn</addtitle><date>2013-06</date><risdate>2013</risdate><volume>242</volume><issue>6</issue><spage>678</spage><epage>686</epage><pages>678-686</pages><issn>1058-8388</issn><eissn>1097-0177</eissn><abstract>ABSTRACT
Background: 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. Results: Here we report that Jagged1 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 Jagged1 in airway epithelium increased the number of ciliated cells at the expense of Clara cells, a phenotype associated with downregulation of Hes1. Deletion of Jagged1 also led to an increased number of pulmonary neuroendocrine cells (PNEC), suggesting that Jagged1/Notch signaling inhibits PNEC cell fate. As expected, Jagged1 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, Jagged1 deletion induced mucous metaplasia, accompanied by downregulation of Hes1 and Hes5. Conclusions: 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. Developmental Dynamics 242:678–686, 2013. © 2013 Wiley Periodicals, Inc.
Key Findings
Jagged1 regulates airway cell fate decision in the developing lung
Jagged1 prevents mucous metaplasia in the postnatal lung
Jagged1 influences alveologenesis</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>23526493</pmid><doi>10.1002/dvdy.23965</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | airway cell fate Animals Calcium-Binding Proteins - genetics Calcium-Binding Proteins - physiology Cell Differentiation Cell Lineage Epithelial Cells - metabolism Gene Expression Regulation, Developmental Immunohistochemistry Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - physiology Jagged-1 Protein Jagged1 lung Lung - embryology Lung - metabolism Membrane Proteins - genetics Membrane Proteins - physiology Mice Mice, Transgenic mucous metaplasia Neuroendocrine Cells - metabolism Notch Phenotype Receptors, Notch - metabolism Serrate-Jagged Proteins Signal Transduction Time Factors |
title | Jagged1 is the major regulator of notch‐dependent cell fate in proximal airways |
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