Cilia take charge in L–R asymmetry
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《细胞学杂志》
Brueckner/Elsevier
Left–right asymmetry is determined by the distinct activities of two populations of cilia in the node of the mouse embryo, according to results from James McGrath, Martina Brueckner (Yale Univesity, New Haven, CT), and colleagues.Previous experiments suggested that ciliary movement at the node generates movement of the extracellular fluid surrounding the node, called nodal flow. Nodal flow is critical for establishing L–R asymmetry and requires the motor protein left–right dynein (lrd). But just what kind of signal could be at work in such a situation was unclear. To find out, Brueckner and her team engineered a mouse expressing GFP-tagged lrd under the control of the wild-type lrd promoter. GFP-lrd is expressed in the central cilia in the node, but is absent from a second population of cilia surrounding those expressing lrd. With the use of videomicroscopy, the team finds that the lrd-expressing cilia are motile, whereas many of the cilia in the surrounding population are nonmotile.
Both populations, however, express polycystin-2, a cation channel that acts as a mechanosensor in the kidney, where fluid currents trigger an influx of calcium. When the Yale team looked at calcium signaling in the node, they found that only those cilia to the left of the motile population induce a rise in intracellular calcium. This asymmetric distribution is disrupted in lrd and polycystin-2 mutants, suggesting that nodal flow produced by the central motile cilia induce calcium influx only in cells in the direction of flow.
"The whole nodal flow hypothesis has been somewhat of a difficult sell, because a major developmental process—formation of one of the three primary body axes—is happening in the extraembryonic space," says Brueckner. "But our model suggests that L–R development is entirely dependent on the physical force created by nodal flow, and its inherent simplicity makes it really satisfying." The next step is to determine how asymmetrically expressed genes like nodal are regulated by calcium signaling.
Reference:
McGrath, J., et al. 2003. Cell. 114:61–73.(Calcium is concentrated on the left side)
Left–right asymmetry is determined by the distinct activities of two populations of cilia in the node of the mouse embryo, according to results from James McGrath, Martina Brueckner (Yale Univesity, New Haven, CT), and colleagues.Previous experiments suggested that ciliary movement at the node generates movement of the extracellular fluid surrounding the node, called nodal flow. Nodal flow is critical for establishing L–R asymmetry and requires the motor protein left–right dynein (lrd). But just what kind of signal could be at work in such a situation was unclear. To find out, Brueckner and her team engineered a mouse expressing GFP-tagged lrd under the control of the wild-type lrd promoter. GFP-lrd is expressed in the central cilia in the node, but is absent from a second population of cilia surrounding those expressing lrd. With the use of videomicroscopy, the team finds that the lrd-expressing cilia are motile, whereas many of the cilia in the surrounding population are nonmotile.
Both populations, however, express polycystin-2, a cation channel that acts as a mechanosensor in the kidney, where fluid currents trigger an influx of calcium. When the Yale team looked at calcium signaling in the node, they found that only those cilia to the left of the motile population induce a rise in intracellular calcium. This asymmetric distribution is disrupted in lrd and polycystin-2 mutants, suggesting that nodal flow produced by the central motile cilia induce calcium influx only in cells in the direction of flow.
"The whole nodal flow hypothesis has been somewhat of a difficult sell, because a major developmental process—formation of one of the three primary body axes—is happening in the extraembryonic space," says Brueckner. "But our model suggests that L–R development is entirely dependent on the physical force created by nodal flow, and its inherent simplicity makes it really satisfying." The next step is to determine how asymmetrically expressed genes like nodal are regulated by calcium signaling.
Reference:
McGrath, J., et al. 2003. Cell. 114:61–73.(Calcium is concentrated on the left side)