Abstract
Follistatin-like 1 (FSTL1) is a secreted bone morphogenetic protein (BMP) antagonist, and it plays a crucial role in normal lung development. Deletion of Fstl1 leads to postnatal death in mice due to respiratory failure. To further explore the role of FSTL1 in mouse lung development, we created a transgene SFTPC-Fstl1 allele mouse displaying significant epithelial overexpression of Fstl1 in all stages of lung development. However, epithelial overexpression of Fstl1 did not alter lung morphogenesis, epithelial differentiation and lung function. Moreover, we found that FSTL1 function was blocked by the epithelial polarization, which was reflected by the remarkable apical secretion of FSTL1 and the basolateral BMP signaling. Taken together, this study demonstrates that tightly spatial interaction of FSTL1 and BMP signaling plays an essential role in lung development.
Highlights
The lung is optimized for oxygen supply of organism
We wondered whether epithelial expression of Fstl1 could rescue the phenotype, since Fstl1 is widely expressed by many tissue types including epithelium during early lung development [15]
The proposed mechanisms of most developmental defects observed in Fstl1 KO mice are related to the disrupted bone morphogenetic protein (BMP) signaling [12,14,27]
Summary
The lung is optimized for oxygen supply of organism. To achieve this goal, the lung consists of two intertwined and precisely branched tree-like tubular systems to conduct air and blood supply. Epithelial-mesenchymal interactions play an essential role in the complicated process of lung development, and such interactions are regulated by a variety of biochemical factors localized in the epithelium or the mesenchyme or both with different patterns of expression [2,3]. BMP4 signaling is crucial for lung development and its activity is tightly regulated by a family of secreted BMP antagonists. Changes of either BMP or BMP-antagonist expression can break the exquisite control system for lung development, resulting in deformities [4,5]. Disruption of BMP4 signaling in lungs of SP-C-dnAlk, SP-C-Xnoggin or SP-C-Gremlin transgenic mice abrogates the proximal-distal patterning in the lung, where differentiation
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