Human lung development can be divided into five stages. At around 4 weeks of gestation, the lung develops as an outgrowth from the ventral wall of the foregut, with trachea subsequently branching into the lobar and segmental bronchi. At approximately 7 weeks of gestation, the airways further branched and epithelial cells differentiated progressively into selleck compound tall pseudostratified columnar epithelium. By 12 weeks, many small tubular structures surrounded by short columnar cells were dis tributed throughout the human lung sections. From 17 weeks of gestation, the short columnar epithelium was replaced progressively by cuboidal cells in a distal to proximal direction. At 21 weeks of gestation, the differ entiation of pneumocytes and some extent of alveoliza tion could be observed in human lung.

All in all, in human lung, 70 % of the total airways generated at birth are formed by 14 W and all of the conducting airways and terminal bronchioles are formed by the end of 17 W. Therefore, it was speculated that most of the canonical WNT signaling components were already Inhibitors,Modulators,Libraries present in the lung buds, but their functions may be pre dominantly involved in branching and division of con duction airway or terminal bronchioles during the pseudoglandular stage. This hy pothesis is also supported by previous reports that the WNT signaling system is not necessary for the establish ment of the primary branching pattern of the lung but is required for appropriate branching morphogenesis.

Analysis of gene expression patterns indicated that all of the canonical WNT/B CATENIN signaling Inhibitors,Modulators,Libraries compo nents were mainly expressed in the peripheral epithe lium, although the canonical WNT signal transducers and transcription Inhibitors,Modulators,Libraries factors were also slightly Inhibitors,Modulators,Libraries scattered into the surrounding mesenchyme in the developing human lung. Correct patterning of lung tissues depends on epithelial mesenchymal cell interactions. Therefore, it is possible that the canonical WNT signals are primar ily transduced into the epithelial cells through WNT receptors and co receptors and then activated by down stream signal transducers and transcription factors both in the peripheral epithelium and mesenchymal cells through epithelial mesenchymal cell interactions. It is also possible that the fast and progressive differentiation of tubular structures and epithelial cells during human lung development results in the slighter and weaker strength of signals in the mesenchyme attained by in situ hybridization, consistent with our previous observations.

CHIR 99021 is one of a new class of highly selective GSK 3 inhibitors that effectively Inhibitors,Modulators,Libraries inhibit GSK 3 activity under many conditions in isolated cells and tissues. In this study, CHIR99021 was used to activate canonical WNT/B CATENIN signaling components in the devel oping human lung. Increased expression of B CATENIN and WNT signal transcription factors and target genes was observed in human or lung tissues after exposure to CHIR 99021. K?nigshoff et al.