Two populations of node monocilia initiate left-right asymmetry in the mouse.
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.
McGrath
James
J
Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Somlo
Stefan
S
Makova
Svetlana
S
Tian
Xin
X
Brueckner
Martina
M
D000818:Animals; D056444:Axonemal Dyneins; D019521:Body Patterning / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D004398:Dyneins / Q000172:deficiency / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D005333:Fetus; D007839:Functional Laterality / Q000502:physiology*; D005775:Gastrula / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D020897:Organizers, Embryonic / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D011993:Recombinant Fusion Proteins; D050396:TRPP Cation Channels
D056444:Axonemal Dyneins; D004398:Dyneins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D050396:TRPP Cation Channels; C402391:Dnah11 protein, mouse