TY - JOUR
T1 - Abnormal development of the intercostal muscles and the rib cage in Myf5-/- embryos leads to pulmonary hypoplasia
AU - Inanlou, Mohammad Reza
AU - Kablar, Boris
PY - 2005/1
Y1 - 2005/1
N2 - 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.
AB - 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.
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U2 - 10.1002/dvdy.20202
DO - 10.1002/dvdy.20202
M3 - Article
C2 - 15580568
AN - SCOPUS:11244318601
SN - 1058-8388
VL - 232
SP - 43
EP - 54
JO - Developmental Dynamics
JF - Developmental Dynamics
IS - 1
ER -