A lthough paired organs such as the kidney and the lung are neatly arranged on each side of the body's midline, other tissues such as the heart and the liver prefer to be on either the left or the right. But how does a developing embryo ensure that, for example, the tube of mesodermal tissue that will eventually form the heart, curves to the left of the body's axis? Recent findings by Okada et al. ([1][1]) add to growing evidence that the clockwise rotation of cilia on embryonic nodal cells is the initial event that determines the asymmetric placement of certain organs. Nodal cells, each bearing a single cilium, are clustered in a triangular pit (node) that first appears as the neural plate is laid down (at day 7.5 of mouse embryonic development). In work published last year ([2][2]), Okada and colleagues reported that in mice lacking either the KIF3A or KIF3B motor protein kinesins, the asymmetry of organ placement was random ([2][2]). These two proteins (together with KAP3) form a complex that transports structural components of the cilium along its hollow interior. Animals deficient in either KIF3A or KIF3B are devoid of cilia. In their new work ([1][1]), the Japanese group decided to investigate why the organs of the iv and inv mutant mouse strains are in abnormal locations. In the iv strain, which carries a mutation in a gene encoding dynein (a component of ciliary architecture), the location of organs is randomly asymmetric, whereas in inv mice (which carry a mutation in the inv gene, whose function is unknown), organ placement is completely reversed. The investigators suspected that a defect in nodal cilia could be the culprit common to both abnormalities. To test their hypothesis, they analyzed movement of nodal cilia with a video fluorescence microscope, following the trajectory of fluorescent beads chemically attached to the ends of the cilia (large green circle in figure). The movement of unattached fluorescent beads (green spots in figure) revealed how ciliary motion altered the flow of extraembryonic fluid in the node. The authors discovered that, unlike nodal cilia in normal mice that rotated clockwise (apparently in synchrony), those in iv mice were motionless. The normal clockwise rotation of nodal cilia moved the fluid to the left of the node but, in the absence of ciliary movement, there was no fluid flow. In inv mice, the cilia appeared to rotate normally, but a closer look revealed that they were moving asynchronously. This, together with an abnormality in the shape of the node, generated turbulence in the fluid flow. ![Figure][3] CREDIT: YASUSHI OKADA Intriguingly, nodal fluid flow begins about the time that left-right determination of tissue location first becomes manifest; asymmetric expression of left- or right-determining genes such as lefty-2 soon follows. The Japanese group speculated that the fluid might contain morphogens (molecules that dictate development of embryonic tissues) that would accumulate on the lefthand side of the node, driven by the clockwise rotation of the cilia. Accumulation of sufficient morphogen would induce expression of genes in ventral node cells, which would then direct expression of left- or right-determining genes in adjacent mesodermal cells (these are the cells that will eventually develop into organs). Next, Okada and collaborators plan to identify the fluid morphogens and to alter left-right determination in mouse embryos by mechanically perturbing fluid flow. 1. [↵][4]1. Y. Okada 2. et al. , Mol. Cell 4, 459 (1999). [OpenUrl][5][CrossRef][6][PubMed][7][Web of Science][8] 2. [↵][9]1. S. Nonaka 2. et al. , Cell 95, 829 (1999). 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