FIG. 2.

Linkage of bioelectrical signals and Ca²⁺ transients to other signaling mechanisms in different biological processes. (A) Biochemical WNT and SHH pathways promote the establishment of Cx43 gap junction network, facilitating the completion of a bioelectric circuit around individual feather buds. The depolarization-induced VGCC activation, the gap junction network, and CRACs contribute to the synchronized Ca²⁺ oscillations in feather mesenchyme. These oscillations may promote cell migration either through transcriptional regulation (NFAT pathway), or MLCK activation to contract the actin/myosin network, or ATP production enhancement in mitochondria. (B) Early chondrogenic differentiation in limb involves ENaC-dependent depolarization, which initiates Cav1.2-dependent Ca²⁺ transients. Meanwhile, some other Ca²⁺ channels have also been reported to initiate Ca²⁺ transients during chondrogenic differentiation. These transients activate NFAT pathway and elevate Sox9 expression. (C) Spontaneous contractions of intestinal smooth muscle cells are driven by propagating waves of Ca²⁺. The formation of these waves requires depolarization-induced VGCC activation and gap junction network-based Ca²⁺ exchange between cells. The cyclic contraction serves as a biomechanical signal aligning newly forming smooth muscle layer along the direction perpendicular to it, likely through modulating actin network and focal adhesions. Cx43, connexin-43; ENaC, epithelial Na⁺ channel; MLCK, myosin light chain kinase; SHH, Sonic Hedgehog; WNT, wingless-INT.