Differential expression of tenascin-C in the developing human lung: an immunohistochemical study

Abstract

Much of the specification for the basic embryonic body plan is the result of a hierarchy of developmental decisions at different developmental times. The extracellular matrix (ECM) appears to be a very dynamic structure during embryogenesis. One of the mesenchymal ECM proteins, tenascin, is reported to be transiently expressed during embryonic tissue development, and is absent or much reduced in most fully developed organs. The respiratory system is an outgrowth of the ventral wall of the foregut, and the epithelium of the larynx, trachea, bronchi and alveoli is of endodermal origin. The cartilaginous and muscular components are of mesodermal origin. The aim of this study was to investigate the role of tenascin-C (TNC) in the developing human lung, during the pseudoglandular, canalicular and saccular stage of lung maturation. Formalin-fixed, paraffin-embedded tissue from the lungs of 30 embryos (10 corresponding to the 10th to the 16th gestational week (pseudoglandular stage), 10 to the 17th to the 23rd gestational week (canalicular stage), and 10 to the 24th to the 27th gestational week (saccular stage), were investigated by conventional histology and immunohistology for the expression levels of TNC. The changes observed in the distribution patterns suggest that during embryogenesis, the rate of tenascin synthesis changes significantly. During the pseudoglandular stage, the density of cells expressing TNC was higher in the condensing mesenchyme surrounding the epithelial glands than in the epithelial cells, whereas the inverse result was observed during the canalicular stage. During the saccular stage the pattern of immunoreactivity with TNC was lower than those of the pseudoglandular and canalicular stage, either in epithelial or mesenchymal cells, but it was highly expressed in the basement membranes. This restricted spatiotemporal distribution suggests that tenascin has a key role (1) in mesenchymal tissue remodeling during the pseudoglandular stage, a period that describes the development of the complete bronchial tree and (2) on the epithelial cell shape and function during the canalicular stage, a period that describes the formation of pneumocytes type I and pneumocytes type II. The later, will produce the surfactant, a phospholipid-rich fluid capable of lowering surface tension at the air-alveolar interface. During the saccular stage, tenascin was present mainly in the basement membranes surrounding the acinar and vascular structures, indicating a supporting and mechanical role.

EngineeringDe NovoAssembly of Fetal Pulmonary Organoids

“…5D) suggests that TN-C is a spatial refiner of VEGF-Adependent endothelial tubular morphogenesis and network formation. TN-C has been implicated in guiding the extension of secondary septa during alveolarization, 37,43 but our correlative observations suggest that it may also guide the apposition of epithelial and endothelial cells at the nascent alveolar-capillary interface (Fig. 4G-I).…”

“…The critical role of TN-C in lung development in vivo has largely been deduced from histological studies 37,38,43 and embryonic lung explant cultures in the context of hypoxia 28 and TN-C gene deletion, 39 all of which demonstrated a positive regulatory role of TN-C in lung epithelial branching morphogenesis. Jones and colleagues demonstrated an indirect functional connection between TN-C and distal lung vascular development through the homeodomain transcription factor Prx-1, which is expressed in the mesenchyme and is required for pulmonary vascular development and TN-C gene expression.…”

“…Focal deposition patterns of TN-C indicate a role in FGF10/7/2-driven morphogenesis Given the known and implicated roles of TN-C in lung development, [37][38][39][40][41][42][43][44] we hypothesized that focal deposition of TN-C could provide pivotal cues for the spatial patterning of histiotypic endothelial and epithelial morphogenesis. Since the starting ECM is a simple, homogeneous type I collagen gel, the presence of TN-C and other ECM constituents, such as laminin (LN), is reflective of endogenous production by fetal pulmonary cells.…”

Extracellular matrix composition in COPD

“…Tenascin and fibronectin are altered in ongoing tissue injury, regulating important cell properties and inflammatory cell chemotaxis [19]. There are few studies analysing the expression of tenascin and fibronectin in COPD patients [13,20,21], but no study has addressed these proteins in all lung compartments.…”

Development of the pulmonary pleura with special reference to the lung surface morphology: a study using human fetuses

“…Matrices in the fetal pulmonary interstitium have been of major interest for embryologists with a focus on epithelial-mesenchymal interactions and epithelio-mesenchymal transitions [14151617]. Some components of the extracellular matrix (ECM), such as tenascin-C and others, are likely to mechanistically support branching and growth of bronchioli [17].…”