Roles of cilia, fluid flow, and Ca2+ signaling in breaking of left–right symmetry

• Left–right symmetry breaking involves cilia in the node.
• Motile cilia generate a unidirectional fluid flow.
• The flow is sensed by immotile cilia via Ca2+ channels.

The emergence of left–right (L–R) asymmetry during embryogenesis is a classic problem in developmental biology. It is only since the 1990s, however, that substantial insight into this problem has been achieved by molecular and genetic approaches. Various genes required for L–R asymmetric morphogenesis in vertebrates have now been identified, and many of these genes are required for the formation and motility of cilia. Breaking of L–R symmetry in the mouse embryo occurs in the ventral node, where two types of cilia are present. Whereas centrally located motile cilia generate a leftward fluid flow, peripherally located immotile cilia sense a flow-dependent signal, which is either chemical or mechanical in nature. Although Ca2+ signaling is implicated in flow sensing, the precise mechanism remains unknown. Here we summarize current knowledge of L–R symmetry breaking in vertebrates (focusing on the mouse), with a special emphasis on the roles of cilia, fluid flow, and Ca2+ signaling.