Contractile activity of skeletal musculature involved in breathing is essential for normal lung cell differentiation, as revealed in Myf5-/-:MyoD-/- embryos.
In the current study, the role of contractile activity of respiratory muscles in fetal lung growth and cell differentiation was examined using Myf5-/-:MyoD-/- mouse embryos. As previously found, Myf5-/-:MyoD-/- mouse embryos had no respiratory musculature. Consequently, they suffered from pulmonary hypoplasia and died shortly after birth. The hypoplastic lung had decreased proliferation and increased apoptotic index as early as embryonic day 14.5. By contrast, only at the last gestational day, the number of lung cells expressing platelet derived growth factor B and insulin growth factor I was decreased, while the gradient of the thyroid transcription factor 1 was not maintained. Type II pneumocytes had a failure in glycogen utilization and surfactant storage and secretion but were able to synthesize the surfactant-associated proteins. Type I pneumocytes were readily detectable using an early differentiation marker (i.e., Gp38). However, the late differentiation of type I pneumocytes never occurred, as revealed by transmission electron microscopy. Together, our findings suggest that pulmonary distension due to fetal breathing-like movements plays an important role not only in lung growth but also in lung cell differentiation.
Inanlou
Mohammad Reza
MR
Dalhousie University, Faculty of Medicine, Department of Anatomy and Neurobiology, Halifax, Nova Scotia, Canada.
Kablar
Boris
B
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000196:embryology / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D051787:Myogenic Regulatory Factor 5; D009929:Organ Size / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D012119:Respiration; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C497417:MYF5 protein, human; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D020574:Proto-Oncogene Proteins c-sis; D015534:Trans-Activators; D020797:Receptor, Platelet-Derived Growth Factor beta