1. Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamada-oka, Suita, Osaka 565-0871, Japan; and CREST, Japan Science and Technology Corporation (JST), Japan

Correspondence to: Shigenori NonakaHiroshi Hamada Correspondence and requests for materials should be addressed to S.N. (e-mail: Email: snonaka@fbs.osaka-u.ac.jp) or H.H. (e-mail: Email: hamada@fbs.osaka-u.ac.jp).

Abstract

Substantial insight has recently been achieved into the mechanisms responsible for the generation of left–right (L–R) asymmetry in the vertebrate body plan^{1, 2, 3, 4}. However, the mechanism that underlies the initial breaking of symmetry has remained unclear. In the mouse, a leftward fluid flow on the ventral side of the node caused by the vortical motion of cilia (referred to as nodal flow) is implicated in symmetry breaking⁵, but direct evidence for the role of this flow has been lacking. Here we describe the development of a system in which mouse embryos are cultured under an artificial fluid flow and with which we have examined how flow affects L–R patterning. An artificial rightward flow that was sufficiently rapid to reverse the intrinsic leftward nodal flow resulted in reversal of situs in wild-type embryos. The artificial flow was also able to direct the situs of mutant mouse embryos with immotile cilia. These results provide the first direct evidence for the role of mechanical fluid flow in L–R patterning.

1. Graduate School of Frontier Biosciences, Osaka University, 1–3 Yamada-oka, Suita, Osaka 565-0871, Japan; and CREST, Japan Science and Technology Corporation (JST), Japan

Correspondence to: Shigenori NonakaHiroshi Hamada Correspondence and requests for materials should be addressed to S.N. (e-mail: Email: snonaka@fbs.osaka-u.ac.jp) or H.H. (e-mail: Email: hamada@fbs.osaka-u.ac.jp).