Cilia-to-Cilia Communication

Many organisms, including humans, exhibit left-right (L-R) asymmetry in addition to bilateral symmetry. Molecular asymmetry, in the form of asymmetrically localized expression of lateralized genes, such as nodal , lefty-2 , and Pitx2 occurs before visible asymmetry. Analysis of genetic mutations affecting asymmetry pointed to microtubules, their associated motors, and cilia as crucial for properly establishing L-R asymmetry. McGrath et al. created mice containing green fluorescent protein (GFP)-tagged left-right dynein (LRD), the product of a gene known to cause L-R asymmetry defects when mutated. Embryos on embryonic day 7.5 (E7.5) were labeled for acetylated tubulin to visualize all cilia, and GFP-LRD was visualized. The node region of the embryo contained two populations of cilia: motile LRD-containing cilia in the center and nonmotile, LRD-lacking cilia in the periphery. All node cilia also expressed the calcium-activated cation channel polycystin-2 (Pkd2), the product of a gene mutated in polycystic kidney disease (mutations in the mouse gene also cause asymmetry defects). During the period (E7.75) that ciliary movement in the node created a flow of the extracellular fluid, a calcium signal was detected in the endodermal cells at the right side of the node only. Perinodal calcium signaling was abnormal in LRD-deficient embryos and absent in pkd2-deficient embryos. Thus, the authors suggest that initial L-R asymmetry is set at the node by the central, motile cilia-generated leftward flow that is sensed in a Pkd2-dependent manner by the peripheral, nonmotile cilia and leads to an asymmetric calcium signal. J. McGrath, S. Somio, S. Makova, X. Tian, M. Brueckner, Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 114 , 61-73 (2003). [Online Journal]