Two Populations of Node Monocilia Initiate Left-Right Asymmetry in the Mouse
نویسندگان
چکیده
The vertebrate body plan has conserved handed left-right (LR) asymmetry that is manifested in the heart, lungs, and gut. Leftward flow of extracellular fluid at the node (nodal flow) is critical for normal LR axis determination in the mouse. Nodal flow is generated by motile node cell monocilia and requires the axonemal dynein, left-right dynein (lrd). In the absence of lrd, LR determination becomes random. The cation channel polycystin-2 is also required to establish LR asymmetry. We show that lrd localizes to a centrally located subset of node monocilia, while polycystin-2 is found in all node monocilia. Asymmetric calcium signaling appears at the left margin of the node coincident with nodal flow. These observations suggest that LR asymmetry is established by an entirely ciliary mechanism: motile, lrd-containing monocilia generate nodal flow, and nonmotile polycystin-2 containing cilia sense nodal flow initiating an asymmetric calcium signal at the left border of the node.
منابع مشابه
Cilia are at the heart of vertebrate left-right asymmetry.
Handed asymmetry of the shape and position of the internal organs is found in all vertebrates, and is essential for normal cardiac development. Recent genetic and embryological experiments in mouse embryos have demonstrated that left-right asymmetry is established by directional flow of extraembryonic fluid surrounding the node, which is driven by motile monocilia.
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ورودعنوان ژورنال:
- Cell
دوره 114 شماره
صفحات -
تاریخ انتشار 2003