Cdonis required for organ Left-Right patterning via regulating DFCs migration and the sequential ciliogenesis

AbstractCdonandbocare members of the cell adhesion molecule subfamily III Ig/fibronectin. Although they were reported to be involved in muscle and neural development at late developmental stage, while their early roles in embryonic development are unknown. Here we discovered that zebrafishcdonbut notbocwas expressed in dorsal forerunner cells (DFCs) and epitheliums of Kupffer’s vesicle (KV), implying the possible role ofcdonin organ LR patterning. Further data showed that the liver and heart LR patterning was disturbed incdonmorphants andcdonmutants. Mechanically, we found thatcdonloss of function led to dispersed DFCs migration, smaller KV and defective ciliogenesis, which resulting in randomizedNodal/spawsignaling and the sequential organ LR patterning defect. Finally, predominant distribution of acdonMO in DFCs led to defects in DFCs migration, KV morphogenesis/ciliogenesis,Nodal/spawsignaling and organ LR asymmetry, being similar to those incdonmorphants andcdon-/-embryos, indicating a cell-autonomous role ofcdonin regulating KV formation and ciliogenesis during LR patterning. In conclusion, our data demonstrated that, during gastrulation stage and early somitogenesis stage,cdonis required for proper DFCs migration, KV formation and ciliogenesis, thus playing an important role in setting up organ LR asymmetry.