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

Cdon and boc are 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 zebrafish cdon but not boc was expressed in dorsal forerunner cells (DFCs) and epitheliums of Kupffers vesicle (KV), implying the possible role of cdon in organ LR patterning. Further data showed that the liver and heart LR patterning was disturbed in cdon morphants and cdon mutants. Mechanically, we found that cdon loss of function led to dispersed DFCs migration, smaller KV and defective ciliogenesis, which resulting in randomized Nodal/spaw signaling and the sequential organ LR patterning defect. Finally, predominant distribution of a cdon MO in DFCs led to defects in DFCs migration, KV morphogenesis/ciliogenesis, Nodal/spaw signaling and organ LR asymmetry, being similar to those in cdon morphants and cdon-/- embryos, indicating a cell-autonomous role of cdon in regulating KV formation and ciliogenesis during LR patterning. In conclusion, our data demonstrated that, during gastrulation stage and early somitogenesis stage, cdon is required for proper DFCs migration, KV formation and ciliogenesis, thus playing an important role in setting up organ LR asymmetry.