Several transcription factors are present in the list, including TGIF1, FOXF2, FOXF1, AATF and PFDN1. Examination of the leading edge gene list between zebrafish swimbladder and mouse lung showed a similar profile (data not shown). The epithelium is the inner most layer of the swimbladder and is in direct contact with the gas inside. It has been shown by transmitted electron microscopy that the swimbladder epithelial cells are polarized even prior to inflation. Tight junctions serve to form seals between epithelial cells, creating a selectively permeable barrier to intercellular diffusion. Consistent with this, our KEGG pathway analysis indicated that the tight junction pathway genes were indeed enriched in the swimbladder. Among the swimbladder enriched gene, the zebrafish homologs of cldn4/ 5/6/7/9 were identified, together with members of the Rho small GTPase subfamily including cdc42, rhoA and rab13. Claudins are transmembrane proteins which act in concert with other transmembrane and peripheral proteins to form the physical basis for tight junction. There are roughly two dozens of different claudins. In human airways, both bronchi and bronchioles express Claudin 1, 3, 4, 5 and 7. Particularly, CLDN3/4/5 have been found to be co-expressed by type II alveolar epithelial cells. It has been revealed by immunofluorescence staining that CLDN4 is increasingly localized to the apical tight junction region, but with lower expression at the lateral region. In contrast, CLDN3 and 5 are localized exclusively in the apical-most region of the tight junctions. Altered Claudin expression pattern can change the paracellular permeability characteristics of the epithelium. For example, CLDN3 overexpression decreases solute permeability, whereas CLDN5 increases permeability. In summary, the expression of CLDN/cldn 4, 5 and 7 is conserved between the human lung and the zebrafish swimbladder. However, cldn9, which is the one of the highest expressed in the swimbladder, is not identified in the human lung. Interestingly, Cldn9 is the most highly expressed in the inner ear of all the Claudin family members, and it is present in all of the major epithelial cell types that line the endolymphatic space.
by a chemical library and four prospective PhoQ inhibitors ended up identified
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