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

Abstract

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.