Fig. 11. Model of Ca_i²⁺ action in laterality. (A) At HH3++/HH4-elevated Ca_i²⁺ (green) appears along the anterior Hensen's node (HN), overlapping with RyR expression; its appearance requires RyR and proton ATPases. A transient depolarization is also observed to the left of Hensen's node (HN) and the primitive streak (PS). Gap junctions (blue dots) may relay and stabilize these early signals. (B) Left-side Ca_i²⁺ enrichment occurs at HH4+/HH5-, and the head process (HP) bifurcates the Ca_i²⁺ field. Shh (dark blue) becomes left-side restricted in the node. Midline expression of serotonin, 5-HT₃, 5-HT₄ and H⁺K+ATPase reduces Ca_i²⁺ and makes a barrier (light blue) for autonomous LR regulation of Ca_i²⁺. (C) By HH6, left Ca_i²⁺ is substantially enriched. Factors including RA, RyR, extracellular calcium and the H⁺V-ATPase sustain left Ca_i²⁺ elevation and Nodal induction, whereas serotonin effectors and the H⁺K⁺-ATPase suppress right Ca_i²⁺. Extracellular calcium activates Notch and supports CICR RyR. See text for details.