Abnormal development of the intercostal muscles and the rib cage in Myf5-/- embryos leads to pulmonary hypoplasia.
The aim of our study was to investigate the importance of pulmonary distension and fetal breathing-like movements executed by the contractile activity of the intercostal respiratory muscles for proper lung growth and maturation. Lung development in Myf5-/- embryos, lacking the rib cage and functional intercostal musculature, was compared with wild-type controls at embryonic days 14.5, 16.5, and 18.5. Our data revealed that Myf5-/- embryos suffered from pulmonary hypoplasia in part due to the decreased number of proliferating lung cells and in part due to the increased number of terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) -positive cells. In addition, the proximal-to-distal expression gradient of thyroid transcription factor-1 observed in wild-type embryos was not maintained in Myf5-/- embryos. The number of lung cells expressing platelet-derived growth factor-BB, its receptor and insulin growth factor-I was significantly decreased in the hypoplastic lung. By contrast, no difference in the expression pattern of surfactant associated proteins or Clara cells marker was detected between wild-type and Myf5-/- embryos. Collectively, our data suggest that the mechanochemical signal transduction pathway used in vitro is also effective in vivo influencing lung growth but not lung cell maturation and resulting in lung hypoplasia. These data affirm the role of fetal breathing-like movements in lung organogenesis.
Inanlou
Mohammad Reza
MR
Dalhousie University, Faculty of Medicine, Department of Anatomy and Neurobiology, Halifax, NS, Canada.
Kablar
Boris
B
D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007366:Intercostal Muscles / Q000196:embryology*; D008168:Lung / Q000166:cytology / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D008171:Lung Diseases / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D009132:Muscles / Q000166:cytology / Q000196:embryology; D051787:Myogenic Regulatory Factor 5; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D015534:Trans-Activators; D000077214:Becaplermin; D007334:Insulin-Like Growth Factor I; D001616:beta-Galactosidase