Role of Junction Plakoglobin in Development of Ciliated Organs

Abstract

Motile cilia play important roles during embryonic development and adult life. In the zebrafish embryo, Junction plakoglobin (Jup) is expressed in organs bearing motile cilia such as the otic vesicle, pronephric duct and Kupffer̓s vesicle that regulates left-right patterning. Jup is a multifunctional armadillo-related molecule that associates with cadherin complexes and participates in signaling cascades. Taking reverse genetic approaches, we found that depletion of Jup disrupted development of the ciliated epithelium in the otic vesicle, pronephric duct and Kupffer̓s vesicle (KV). Using KV as a model organ, we identified a defect in an early step of ciliated epithelium formation. During epithelialization, precursors called dorsal forerunner cells (DFCs) form puncta that contain apical membrane and junction proteins at cell-cell interfaces. DFCs then undergo rearrangements that bring these puncta or contact foci into close proximity with one another to form the center of a rosette structure that gives rise to the nascent KV lumen. Jup depletion disrupted positioning of contact foci and formation of the rosette structure, suggesting Jup regulates cellular rearrangements that drive cohesion of contact foci during epithelium development. These results provide an entry point to dissect a new pathway that mediates morphogenesis of ciliated organs.