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NPAS1 regulates branching morphogenesis in embryonic lung.

Publication ,  Journal Article
Levesque, BM; Zhou, S; Shan, L; Johnston, P; Kong, Y; Degan, S; Sunday, ME
Published in: Am J Respir Cell Mol Biol
April 2007

Drosophila trachealess (Trl), master regulator of tracheogenesis, has no known functional mammalian homolog. We hypothesized that genes similar to trachealess regulate lung development. Quantitative (Q)RT-PCR and immunostaining were used to determine spatial and temporal patterns of npas1 gene expression in developing murine lung. Immunostaining for alpha-smooth muscle actin demonstrated myofibroblasts, and protein gene product (PGP)9.5 identified neuroendocrine cells. Branching morphogenesis of embryonic lung buds was analyzed in the presence of antisense or sense oligodeoxynucleotides (ODN). Microarray analyses were performed to screen for changes in gene expression in antisense-treated lungs. QRT-PCR was used to validate the altered expression of key genes identified on the microarrays. We demonstrate that npas1 is expressed in murine embryonic lung. npas1 mRNA peaks early at Embryonic Day (E)10.5-E11.5, then drops to low levels. Sequencing verifies the identity of npas1 transcripts in embryonic lung. NPAS1 immunostaining occurs in nuclei of parabronchial mesenchymal cells, especially at the tracheal bifurcation. Arnt, the murine homolog of Tango (the heterodimerization partner for Trl) is also expressed in developing lung but at constant levels. npas1- or arnt-antisense ODN inhibit lung branching morphogenesis, with altered myofibroblast development and increased pulmonary neuroendocrine cells. On microarrays, we identify > 50 known genes down-regulated by npas1-antisense, including multiple genes regulating cell migration and cell differentiation. QRT-PCR confirms significantly decreased expression of the neurogenic genes RBP-Jk and Tle, and three genes involved in muscle development: beta-ig-h3, claudin-11, and myocardin. Npas1 can regulate myofibroblast distribution, branching morphogenesis, and neuroendocrine cell differentiation in murine embryonic lung.

Duke Scholars

Published In

Am J Respir Cell Mol Biol

DOI

ISSN

1044-1549

Publication Date

April 2007

Volume

36

Issue

4

Start / End Page

427 / 434

Location

United States

Related Subject Headings

  • Respiratory System
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Oligodeoxyribonucleotides, Antisense
  • Neurons
  • Nerve Tissue Proteins
  • Muscle Cells
  • Morphogenesis
  • Microarray Analysis
  • Mice
 

Citation

APA
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ICMJE
MLA
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Levesque, B. M., Zhou, S., Shan, L., Johnston, P., Kong, Y., Degan, S., & Sunday, M. E. (2007). NPAS1 regulates branching morphogenesis in embryonic lung. Am J Respir Cell Mol Biol, 36(4), 427–434. https://doi.org/10.1165/rcmb.2006-0314OC
Levesque, Bernadette M., Shutang Zhou, Lin Shan, Pamela Johnston, Yanping Kong, Simone Degan, and Mary E. Sunday. “NPAS1 regulates branching morphogenesis in embryonic lung.Am J Respir Cell Mol Biol 36, no. 4 (April 2007): 427–34. https://doi.org/10.1165/rcmb.2006-0314OC.
Levesque BM, Zhou S, Shan L, Johnston P, Kong Y, Degan S, et al. NPAS1 regulates branching morphogenesis in embryonic lung. Am J Respir Cell Mol Biol. 2007 Apr;36(4):427–34.
Levesque, Bernadette M., et al. “NPAS1 regulates branching morphogenesis in embryonic lung.Am J Respir Cell Mol Biol, vol. 36, no. 4, Apr. 2007, pp. 427–34. Pubmed, doi:10.1165/rcmb.2006-0314OC.
Levesque BM, Zhou S, Shan L, Johnston P, Kong Y, Degan S, Sunday ME. NPAS1 regulates branching morphogenesis in embryonic lung. Am J Respir Cell Mol Biol. 2007 Apr;36(4):427–434.

Published In

Am J Respir Cell Mol Biol

DOI

ISSN

1044-1549

Publication Date

April 2007

Volume

36

Issue

4

Start / End Page

427 / 434

Location

United States

Related Subject Headings

  • Respiratory System
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Oligodeoxyribonucleotides, Antisense
  • Neurons
  • Nerve Tissue Proteins
  • Muscle Cells
  • Morphogenesis
  • Microarray Analysis
  • Mice