Cilia Spoil Symmetry in Growing Embryos

3 July 2002 (All day)

Against the flow. Reversing the fluid that flows past young embryos can reverse the embryo's left-right layout.

Our bodies may look symmetric from the outside, but inside, organs such as the heart or the liver are tucked or oriented to the left or right. New research suggests that fluid driven by tiny swirling hairs called cilia may activate certain genes in the growing embryo that lay the groundwork for this asymmetry.

Based on experiments with mice, some scientists had speculated that cilia nestled in a dimple at the top of the embryo called the node might push fluid down the left side of the embryo, carrying a signal that somehow triggers certain genes to activate. Other scientists doubted the idea.

The new experiments suggest that the cilia-driven flow is indeed important. Researchers led by developmental biologist Hiroshi Hamada at the University of Osaka used a pump to reverse the normal leftward flow of fluid over mouse embryos. This caused two key genes normally activated solely on the left side of the body to be expressed on the right side, the team reports in the 4 July issue of Nature. Additional evidence comes from an experiment on mutant mice with crippled cilia. When these mice develop, their internal organs and patterns of gene expression fall randomly into left- or right-oriented layouts. But when the researchers placed the embryos in fluid flowing to the left, they developed normal patterns of gene expression and heart development.

"It's an amazing result," says cell biologist Mark Mercola of Harvard Medical School in Boston. The work shows that the flow is a critical step in left-right patterning, he says, although he adds, "the million-dollar question is what is being swished by the nodal flow." In addition, he cautions that cilia-driven flow may not be a universal first step, as some evidence suggests that left-right differences in some animals begin before the formation of the node and cilia.

Related sites
Hiroshi Hamada's site
Mouse Embryo Development movie from University of New South Wales
Left-Right Asymmetry research in Mark Mercola's Lab

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