Lung development in laminin gamma2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation.
BACKGROUND
Laminin gamma2 (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 gamma2 in lung development has been hypothesized. Targeted deletion of the laminin gamma2 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.


CONCLUSIONS
These findings indicate that laminin gamma2 and laminin-332, despite their prominence in the lung, have a minimal role in lung development through the saccular stage.
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. nnguyen@im.wustl.edu
Nguyet M
NM
Nguyen
Leena
L
Pulkkinen
Jessica A
JA
Schlueter
Guerrino
G
Meneguzzi
Jouni
J
Uitto
Robert M
RM
Senior
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism*; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D002454:Cell Differentiation; D016922:Cellular Senescence; D042783:Endothelial Cells; D004847:Epithelial Cells / Q000473:pathology; D022002:Hemidesmosomes / Q000378:metabolism; D007797:Laminin / Q000172:deficiency* / Q000378:metabolism; D008168:Lung / Q000254:growth & development* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D032389:Myocytes, Smooth Muscle
C498522:Lamc2 protein, mouse; D007797:Laminin