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.

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.

Abnormal development of the diaphragm in mdx:MyoD-/-(9th) embryos leads to pulmonary hypoplasia.

In vitro studies have shown that mechanical factors play an important role in cell cycle kinetics and cell differentiation of the lung through an unknown mechanochemical signal transduction pathway. In this study we evaluated the in vivo role of mechanical factors due to fetal breathing movements (primarily executed by the diaphragm, which is the main respiratory muscle) on lung growth and development by using genetically engineered embryos. Lung growth and development of wild-type, mdx:MyoD+/-(9th) (in which the diaphragm develops normally) and mdx:MyoD-/-(9th) (in which the diaphragm muscle is significantly thinned and not functional) embryos were compared at embryonic day 18.