Fig. 5.

Proposed model for the possible molecular interplay between BMP and Ca²⁺-mediated electrical activity pathways during spinal cord development. Binding of BMP to its receptor activates p38 MAPK, which phosphorylates and negatively modulates Na_v activity. This process diminishes the probability of spontaneous Na_v-mediated membrane depolarizing events and, hence, prevents further activation of Ca_v resulting in a decrease in Ca²⁺ spikes. In turn, Ca²⁺ spikes activate Erk1/2 and decrease the level of nuclear P-tail-Smad. The interaction between Ca²⁺ spike activity and BMP signaling regulates the differentiation of the commissural dorsal spinal phenotype.