Cardiotrophin-1, a cytokine present in embryonic muscle, supports long- term survival of spinal motoneurons

The muscle-derived factors required for survival of embryonic motoneurons are not clearly identified. Cardiotrophin-1 (CT-1), a cytokine related to ciliary neurotrophic factor (CNTF), is expressed at high levels in embryonic limb bud and is secreted by differentiated myotubes. In vitro, CT- 1 kept 43% of purified E14 rat motoneurons alive for 2 weeks (EC₅₀ = 20 pM). In vivo, CT-1 protected neonatal sciatic motoneurons against the effects of axotomy. CT-1 action on motoneurons was inhibited by phosphatidylinositol- specific phospholipase C (PIPLC), suggesting that CT-1 may act through a GPI- linked component. Since no binding of CT-1 to CNTFRα was detected, CT-1 may use a novel cytokine receptor α subunit. CT-1 may be important in normal motoneuron development and as a potential tool for slowing motoneuron degeneration in human diseases.