Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung

Qiwei Yang, Kosuke Ota, Yufeng Tian, Anil Kumar, Jun Wada, Naoki Kashihara, Elisabeth Wallner, Yashpal S. Kanwar

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Fibrillin-2 is an extracellular matrix protein. It is associated with elastic fibers in several tissues and is believed to serve as a ligand for αvβ3 integrin, the latter being a known morphogen. In this study, the role of fibrillin-2 in lung development was investigated. Also, rat fibrillin-2 cDNA was isolated and sequenced and its spatiotemporal expression determined. It had ~88% homology with human fibrillin-2 and had Ca2+ binding epidermal growth factor-like domains, transforming growth factor-β binding protein motifs, and two RGD binding sites. Northern blot analysis revealed an ~10-kb transcript, and fibrillin-2 expression was developmentally regulated, and it paralleled that of tropoelastin. At day 13 of gestation, fibrillin-2 was expressed in the mesenchyme and at the epithelial:mesenchymal interface. From day 13 to 19 of gestation, its expression intensified and was confined around the tracheobronchial airways, while it lessened during the postnatal period. Immunoprecipitation revealed an ~350-kDa band by SDS-PAGE. Treatment with fibrillin-2 antisense oligodeoxynucleotide induced dysmorphogenesis of the lung explants. They were smaller and had rudimentary lung bud branches, collapsed conducting airways, and loose expanded mesenchyme. Concomitantly, fibrillin-2 mRNA, antibody reactivity in the explants, and fibrillin-2- specific radioincorporation were reduced. Anti-αv and -laminin antibody reactivity and their respective incorporated specific radioactivities were unaltered. These data indicate that fibrillin-2 modulates organogenesis of the lung in the context of epithelial:mesenchymal interactions. Conceivably, the collapse of the conducting airways may also be related to the perturbed biology of the fibrillin-2 interacting protein, i.e., elastin, the latter being critical for the normal biophysiology of the lungs.

Original languageEnglish (US)
Pages (from-to)229-242
Number of pages14
JournalDevelopmental Biology
Volume212
Issue number1
DOIs
StatePublished - Aug 1 1999

Keywords

  • CDNA cloning
  • Extracellular matrix
  • Fibrillin
  • Lung development

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung'. Together they form a unique fingerprint.

  • Cite this

    Yang, Q., Ota, K., Tian, Y., Kumar, A., Wada, J., Kashihara, N., Wallner, E., & Kanwar, Y. S. (1999). Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung. Developmental Biology, 212(1), 229-242. https://doi.org/10.1006/dbio.1999.9331