Reemployment of Kupffer's vesicle cells into axial and paraxial mesoderm via transdifferentiation

Kupffers vesicle (KV) in the teleost embryo is a fluid-filled vesicle surrounded by a layer of epithelial cells with rotating primary cilia. KV transiently acts as the left-right organizer but degenerates after the establishment of left-right asymmetric gene expression. Previous labelling experiments indicated that descendants of KV-epithelial cells are incorporated into mesodermal tissues after KV collapses (KV-collapse) in zebrafish embryos. However, the overall picture of their differentiation potency had been unclear due to the lack of suitable genetic tools and molecular analyses. In the present study, we established a novel zebrafish transgenic line with a promoter of charon, in which all KV-epithelial cells and their descendants are specifically labelled until the larval stage. We found that KV-epithelial cells underwent epithelial-mesenchymal transition upon KV-collapse and infiltrate into adjacent mesodermal progenitors, the presomitic mesoderm and chordoneural hinge. Once incorporated, the descendants of KV-epithelial cells expressed distinct mesodermal differentiation markers and contributed to the mature populations such as the axial muscles and notochordal sheath through normal developmental process. These results indicate that fully differentiated KV-epithelial cells possess unique plasticity in that they are reemployed into mesodermal lineages through transdifferentiation after they complete their initial role in KV.