Microarray analysis of Myf5-/-:MyoD-/- hypoplastic mouse lungs reveals a profile of genes involved in pneumocyte differentiation.
Fetal breathing-like movements (FBMs) are important in normal lung growth and pneumocyte differentiation. In amyogenic mouse embryos (designated as Myf5-/-:MyoD-/-, entirely lacking skeletal musculature and FBMs), type II pneumocytes fail to differentiate into type I pneumocytes, the cells responsible for gas exchange, and the fetuses die from asphyxia at birth. Using oligonucleotide microarrays, we compared gene expression in the lungs of Myf5-/-:MyoD-/- embryos to that in normal lungs at term. Nine genes were found to be up-regulated and 54 down-regulated at least 2-fold in the lungs of double-mutant embryos. Since many down-regulated genes are involved in lymphocyte function, immunohistochemistry was employed to study T- and B-cell maturity in the thymus and spleen. Our findings of normal lymphocyte maturity implied that the down-regulation was specific to the double-mutant lung phenotype and not to its immune system. Immunostaining also revealed altered distribution of transcription and growth factors (SATB1, c-Myb, CTGF) from down-regulated genes whose knockouts are now known to undergo embryonic or neonatal death secondary to respiratory failure. Together, it appears that microarray analysis has identified a profile of genes potentially involved in pneumocyte differentiation and therefore in the mechanisms that may be implicated in the mechanochemical signal transduction pathways underlying FBMs-dependent pulmonary hypoplasia.
Baguma-Nibasheka
M
M
Dalhousie University, Faculty of Medicine, Department of Anatomy and Neurobiology, Halifax, NS, Canada.
Angka
H E
HE
Inanlou
M R
MR
Kablar
B
B
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D055513:Connective Tissue Growth Factor; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008171:Lung Diseases / Q000196:embryology / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D051787:Myogenic Regulatory Factor 5 / Q000172:deficiency* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D015656:Respiratory Mechanics; D012132:Respiratory Muscles / Q000196:embryology; D013997:Time Factors
C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D036961:Matrix Attachment Region Binding Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051787:Myogenic Regulatory Factor 5; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; C469541:Satb1 protein, mouse; D055513:Connective Tissue Growth Factor