Determination of left–right patterning of the mouse embryo by artificial nodal flow
- 1 July 2002
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 418 (6893), 96-99
- https://doi.org/10.1038/nature00849
Abstract
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.This publication has 17 references indexed in Scilit:
- Establishment of vertebrate left–right asymmetryNature Reviews Genetics, 2002
- Two-Step Regulation of Left–Right Asymmetric Expression of Pitx2: Initiation by Nodal Signaling and Maintenance by Nkx2Molecular Cell, 2001
- Chlamydomonas IFT88 and Its Mouse Homologue, Polycystic Kidney Disease Gene Tg737, Are Required for Assembly of Cilia and FlagellaThe Journal of cell biology, 2000
- Mechanisms of Left–Right Determination in VertebratesCell, 2000
- Two closely‐related left‐right asymmetrically expressed genes, lefty‐1 and lefty‐2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryosGenes to Cells, 1997
- Conserved left–right asymmetry of nodal expression and alterations in murine situs inversusNature, 1996
- Left–right asymmetric expression of the TGFβ-family member lefty in mouse embryosNature, 1996
- Relationship between asymmetric nodal expression and the direction of embryonic turningNature, 1996
- Morphogenesis of the murine node and notochordal plateDevelopmental Dynamics, 1994
- Critical period of rat development when sidedness of asymmetric body structures is determinedTeratology, 1991