Inversion of Sonic hedgehog action on its canonical pathway by electrical activity

Morphogenic proteins drive the formation and patterning of tissues during embryonic development. Once tissues are formed, their cells progressively differentiate to perform the required specialized functions of the maturing tissue. Whether this transition is accompanied by changes in morphogen signaling remains unclear. Here we identify a striking inversion in Sonic hedgehog (Shh) action on its canonical Gli-dependent pathway driven by the emerging electrical activity in differentiating spinal neurons. This mechanism may allow for switching off Shh proliferative action and thus may prevent pediatric brain tumor formation and occurrence of neurodevelopmental defects.