Figure 5.
A model integrating NaV in regeneration. By 6 hpa, the H+ pump V-ATPase is expressed in the regeneration bud where it regulates the membrane voltage of the bud. V-ATPase activation results in the upregulation of NaV1.2 by 18 hpa. Ablation of NaV1.2 expression (RNAi) or NaV function (pharmacological treatment) inhibits regeneration. NaV activity enables sodium ions to enter regeneration bud cells and, potentially through SIK, to activate downstream pathways (such as BMP and Notch) by 24 hpa, driving regenerative outgrowth and patterning. By 7 d after injury, the rebuilding of the tail is largely complete. Importantly, monensin-mediated induction of a transient sodium flux into nonregenerative buds is sufficient to restore full tail regeneration, demonstrating that intracellular sodium signaling is a key regulator of regeneration able to initiate repair even after a nonregenerative wound epithelium has formed.