State-dependent signaling by Ca_v1.2 regulates hair follicle stem cell function

The signals regulating stem cell activation during tissue regeneration remain poorly understood. We investigated the baldness associated with mutations in the voltagegated calcium channel (VGCC) Ca_v1.2 underlying Timothy syndrome (TS). While hair follicle stem cells express Ca_v1.2, they lack detectable voltage-dependent calcium currents. Ca_v1.2^TS acts in a dominant-negative manner to markedly delay anagen, while L-type channel blockers act through Ca_v1.2 to induce anagen and overcome the TS phenotype. Ca_v1.2 regulates production of the bulgederived BMP inhibitor follistatin-like1 (Fstl1), derepressing stemcell quiescence. Our findings show how channels act in nonexcitable tissues to regulate stem cells and may lead to novel therapeutics for tissue regeneration.