The research group of Associate Professor Shigenori Nonaka and researcher

Daisuke Takao, Laboratory for Spatiotemporal Regulations at NIBB, have found out an asymmetric distribution of dynamic calcium signals in the node of mouse embryo during left-right axis formation.

 In the node of the mouse embryo, rotational movements of cilia generate an external liquid flow known as nodal flow, which determines left-right asymmetric gene expression. How nodal flow is converted into asymmetric gene expression is still controversial, but the increase of Ca²⁺ levels in endodermal cells to the left of the node has been proposed to play a role.However, Ca²⁺ signals inside the node itself have not yet been described.

 Using an optimized Ca²⁺ imaging method, the group was able to observe dynamic Ca²⁺ signals in the node in live mouse embryos. Pharmacological disruption of Ca²⁺ signals did not affect ciliary movements or nodal flow, but did alter the expression patterns of the Nodal and Cerl-2 genes. Quantitative analyses of Ca²⁺ signal frequencies and distributions showed that during left-right axis establishment, formerly symmetric Ca²⁺ signals became biased to the left side. In iv/iv mutant embryos that showed randomized laterality due to ciliary immotility, Ca²⁺ signals were found to be variously left-sided, right-sided, or bilateral, and thus symmetric on average. In Pkd2 mutant embryos, which lacked polycystin-2, a Ca²⁺-permeable cation channel necessary for left-right axis formation, the Ca²⁺ signal frequency was lower than in wild-type embryos. These data support a model in which dynamic Ca²⁺ signals in the node are involved in left-right patterning.

Dr. Daisuke Takao