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Determination of left–right patterning of the mouse embryo by artificial nodal flow


Substantial insight has recently been achieved into the mechanisms responsible for the generation of left–right (L–R) asymmetry in the vertebrate body plan1,2,3,4. 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.

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Figure 1: Flow culture system.
Figure 2: Reversal of the intrinsic nodal flow by fast, but not by slow, rightward artificial flow.
Figure 3: Reversal of situs of wild-type embryos at the presomite stage by fast rightward flow.
Figure 4: Determination of situs of iv/iv embryos by artificial fluid flow.


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We thank I. Minoura for helpful discussion of hydrodynamics and K. Mochida and other members of the Hamada laboratory for technical help and valuable comments. This work was supported by CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation. S.N. was supported by CREST and by a fellowship from the Japan Society for the Promotion of Science for Japanese Junior Scientists.

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Correspondence to Shigenori Nonaka or Hiroshi Hamada.

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Nonaka, S., Shiratori, H., Saijoh, Y. et al. Determination of left–right patterning of the mouse embryo by artificial nodal flow. Nature 418, 96–99 (2002).

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