Tenascin-C in rat lung: distribution, ontogeny and role in branching morphogenesis.
Extracellular matrix is important to organogenesis and may function by modifying cellular adhesion, motility, proliferation, and differentiation. Tenascin-C (TN-C) is a matrix molecule reported to bind some cell lines and to inhibit adhesion of some cell types to fibronectin. This report describes the ontogeny and possible functions of TN-C expression in fetal and newborn rat lung. There was a moderate concentration of TN-C protein at the epithelial-mesenchymal interface during fetal lung development in the period of branching morphogenesis. There was a remarkable accumulation of TN-C during the first postnatal week when alveolarization peaked, followed by a decline to barely detectable levels after the third postnatal week when alveolarization was essentially completed. Loss of TN-C protein followed quickly the loss of TN-C mRNA, suggesting a rapid turnover of TN-C in the extracellular matrix. By light microscopy, immunoreactive TN-C was present in early postnatal lung at the epithelial-mesenchymal interface and was distributed throughout lung mesenchyme. Electron microscopic immunocytochemistry showed TN-C was not a part of the basal lamina and that its lung localization was punctate and different from the uniform distribution of laminin. Antiserum to TN-C significantly inhibited branching morphogenesis of fetal lung explants but did not block their growth. Three bacterially expressed segments of TN-C comprising different fibronectin type III domains inhibited branching morphogenesis as effectively as did antiserum, but an expression protein of the carboxyterminal fibrinogen-like segment had no effect. We conclude that TN-C is expressed in a spatio-temporal pattern consistent with a role in lung development and our in vitro studies indicated a functional role for TN-C during lung branching morphogenesis.
Young
S L
SL
Research Service, Durham VA Medical Center, North Carolina.
Chang
L Y
LY
Erickson
H P
HP
D000367:Age Factors; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D046508:Culture Techniques; D016326:Extracellular Matrix Proteins / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D005260:Female; D008168:Lung / Q000737:chemistry* / Q000254:growth & development; D016253:Microscopy, Immunoelectron; D009024:Morphogenesis; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019063:Tenascin
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D019063:Tenascin