Document Type
Article
Publication Date
2-16-2006
Abstract
Background
Laminin γ2 (Lamc2), one of the polypeptides in laminin-332 (laminin-5), is prominent in the basement membrane of alveolar walls and airways of developing and adult lung. Laminins are important for lung morphogenesis and based on its localization, a function for laminin γ2 in lung development has been hypothesized. Targeted deletion of the laminin γ2 gene in mice results in skin blistering and neonatal death at 3–5 days after birth due to failure to thrive.
Methods
Examination of lung development in Lamc2-/- mice through 1–2 days postnatal was accomplished by morphometric analysis, lung bud culture, electron microscopy, immunohistochemical and immunofluorescence staining.
Results
Compared to littermate controls, Lamc2-/- lungs were similar in morphology during embryonic life. At post-natal day 1–2, distal saccules were mildly dilated by chord length measurements. Epithelial differentiation as evaluated by immunohistochemical staining for markers of ciliated cells, Clara cells, alveolar type I cells and alveolar type II cells did not reveal a difference between Lamc2-/- and littermate control lungs. Likewise, vascular development, smooth muscle cell differentiation, and elastic fiber formation looked similar, as did airway basement membrane ultrastructure. Branching morphogenesis by lung bud culture was similar in Lamc2-/- and littermate control lungs. Since laminin-332 is important for hemidesmosome formation, we examined the structure of tracheal hemidesmosomes by transmission electron microscopy. Compared to littermate controls, Lamc2-/- tracheal hemidesmosomes were less organized and lacked the increased electron density associated with the basement membrane abutting the hemidesmosome.
Conclusion
These findings indicate that laminin γ2 and laminin-332, despite their prominence in the lung, have a minimal role in lung development through the saccular stage.
Recommended Citation
Nguyen, Nguyet M.; Pulkkinen, Leena; Schlueter, Jessica A.; Meneguzzi, Guerrino; Uitto, Jouni; and Senior, Robert M., "Lung development in laminin γ2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation" (2006). Department of Dermatology and Cutaneous Biology Faculty Papers. Paper 1.
https://jdc.jefferson.edu/dcbfp/1
Comments
This article has been peer reviewed. It was published in Respiratory Research 2006, 7:28, under the Creative Commons Attribution license. (Publisher's URL: http://respiratory-research.com/content/7/1/28)