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Targeted Disruption of NeuroD, a Proneural Basic Helix-Loop-Helix Factor, Impairs Distal Lung Formation and Neuroendocrine Morphology in the Neonatal Lung

Despite the importance of airspace integrity in vertebrate gas exchange, the molecular pathways that instruct distal lung formation are poorly understood. Recently, we found that fibrillin-1 deficiency in mice impairs alveolar formation and recapitulates the pulmonary features of human Marfan syndro...

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Autores principales: Neptune, Enid R., Podowski, Megan, Calvi, Carla, Cho, Jang-Hyeon, Garcia, Joe G. N., Tuder, Rubin, Linnoila, R. Ilona, Tsai, Ming-Jer, Dietz, Harry C.
Formato: Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475704/
https://www.ncbi.nlm.nih.gov/pubmed/18339630
http://dx.doi.org/10.1074/jbc.M708692200
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author Neptune, Enid R.
Podowski, Megan
Calvi, Carla
Cho, Jang-Hyeon
Garcia, Joe G. N.
Tuder, Rubin
Linnoila, R. Ilona
Tsai, Ming-Jer
Dietz, Harry C.
author_facet Neptune, Enid R.
Podowski, Megan
Calvi, Carla
Cho, Jang-Hyeon
Garcia, Joe G. N.
Tuder, Rubin
Linnoila, R. Ilona
Tsai, Ming-Jer
Dietz, Harry C.
author_sort Neptune, Enid R.
collection PubMed
description Despite the importance of airspace integrity in vertebrate gas exchange, the molecular pathways that instruct distal lung formation are poorly understood. Recently, we found that fibrillin-1 deficiency in mice impairs alveolar formation and recapitulates the pulmonary features of human Marfan syndrome. To further elucidate effectors involved in distal lung formation, we performed expression profiling analysis comparing the fibrillin-1-deficient and wild-type developing lung. NeuroD, a basic helix-loop-helix transcription factor, fulfilled the expression criteria for a candidate mediator of distal lung development. We investigated its role in murine lung development using genetically targeted NeuroD-deficient mice. We found that NeuroD deficiency results in both impaired alveolar septation and altered morphology of the pulmonary neuroendocrine cells. NeuroD-deficient mice had enlarged alveoli associated with reduced epithelial proliferation in the airway and airspace compartments during development. Additionally, the neuroendocrine compartment in these mice manifested an increased number of neuroepithelial bodies but a reduced number of solitary pulmonary neuroendocrine cells in the neonatal lung. Overexpression of NeuroD in a murine lung epithelial cell line conferred a neuroendocrine phenotype characterized by the induction of neuroendocrine markers as well as increased proliferation. These results support an unanticipated role for NeuroD in the regulation of pulmonary neuroendocrine and alveolar morphogenesis and suggest an intimate connection between the neuroendocrine compartment and distal lung development.
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spelling pubmed-24757042008-09-22 Targeted Disruption of NeuroD, a Proneural Basic Helix-Loop-Helix Factor, Impairs Distal Lung Formation and Neuroendocrine Morphology in the Neonatal Lung Neptune, Enid R. Podowski, Megan Calvi, Carla Cho, Jang-Hyeon Garcia, Joe G. N. Tuder, Rubin Linnoila, R. Ilona Tsai, Ming-Jer Dietz, Harry C. J Biol Chem Molecular Basis of Cell and Developmental Biology Despite the importance of airspace integrity in vertebrate gas exchange, the molecular pathways that instruct distal lung formation are poorly understood. Recently, we found that fibrillin-1 deficiency in mice impairs alveolar formation and recapitulates the pulmonary features of human Marfan syndrome. To further elucidate effectors involved in distal lung formation, we performed expression profiling analysis comparing the fibrillin-1-deficient and wild-type developing lung. NeuroD, a basic helix-loop-helix transcription factor, fulfilled the expression criteria for a candidate mediator of distal lung development. We investigated its role in murine lung development using genetically targeted NeuroD-deficient mice. We found that NeuroD deficiency results in both impaired alveolar septation and altered morphology of the pulmonary neuroendocrine cells. NeuroD-deficient mice had enlarged alveoli associated with reduced epithelial proliferation in the airway and airspace compartments during development. Additionally, the neuroendocrine compartment in these mice manifested an increased number of neuroepithelial bodies but a reduced number of solitary pulmonary neuroendocrine cells in the neonatal lung. Overexpression of NeuroD in a murine lung epithelial cell line conferred a neuroendocrine phenotype characterized by the induction of neuroendocrine markers as well as increased proliferation. These results support an unanticipated role for NeuroD in the regulation of pulmonary neuroendocrine and alveolar morphogenesis and suggest an intimate connection between the neuroendocrine compartment and distal lung development. American Society for Biochemistry and Molecular Biology 2008-07-25 /pmc/articles/PMC2475704/ /pubmed/18339630 http://dx.doi.org/10.1074/jbc.M708692200 Text en Copyright © 2008, The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
spellingShingle Molecular Basis of Cell and Developmental Biology
Neptune, Enid R.
Podowski, Megan
Calvi, Carla
Cho, Jang-Hyeon
Garcia, Joe G. N.
Tuder, Rubin
Linnoila, R. Ilona
Tsai, Ming-Jer
Dietz, Harry C.
Targeted Disruption of NeuroD, a Proneural Basic Helix-Loop-Helix Factor, Impairs Distal Lung Formation and Neuroendocrine Morphology in the Neonatal Lung
title Targeted Disruption of NeuroD, a Proneural Basic Helix-Loop-Helix Factor, Impairs Distal Lung Formation and Neuroendocrine Morphology in the Neonatal Lung
title_full Targeted Disruption of NeuroD, a Proneural Basic Helix-Loop-Helix Factor, Impairs Distal Lung Formation and Neuroendocrine Morphology in the Neonatal Lung
title_fullStr Targeted Disruption of NeuroD, a Proneural Basic Helix-Loop-Helix Factor, Impairs Distal Lung Formation and Neuroendocrine Morphology in the Neonatal Lung
title_full_unstemmed Targeted Disruption of NeuroD, a Proneural Basic Helix-Loop-Helix Factor, Impairs Distal Lung Formation and Neuroendocrine Morphology in the Neonatal Lung
title_short Targeted Disruption of NeuroD, a Proneural Basic Helix-Loop-Helix Factor, Impairs Distal Lung Formation and Neuroendocrine Morphology in the Neonatal Lung
title_sort targeted disruption of neurod, a proneural basic helix-loop-helix factor, impairs distal lung formation and neuroendocrine morphology in the neonatal lung
topic Molecular Basis of Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475704/
https://www.ncbi.nlm.nih.gov/pubmed/18339630
http://dx.doi.org/10.1074/jbc.M708692200
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