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The homeoprotein ENGRAILED-1 promotes motoneuron survival and sustains motor functions

Vargas Abonce, S. E.; Leboeuf, M.; Moya, K. L.; Prochiantz, A. L.

2019-08-13 neuroscience
10.1101/734020 bioRxiv
Show abstract

Motoneuron degeneration leads to skeletal muscle denervation and impaired motor functions, yet the signals involved remain poorly understood. We find that extracellular ENGRAILED-1, a homeoprotein expressed in spinal cord V1 interneurons that synapse on -motoneurons, has non-cell autonomous activity. Mice heterozygote for Engrailed-1 develop muscle weakness, abnormal spinal reflex and partial neuromuscular junction denervation. A single intrathecal injection of ENGRAILED-1 restores innervation, limb strength, extensor reflex and prevents lumbar -motoneuron death for several months. The autophagy gene p62, which was found to network with Engrailed-1 and amyotrophic lateral sclerosis genes, is misregulated in Engrailed-1 heterozygote mice -motoneurons and is rescued following ENGRAILED-1 injection. These results identify ENGRAILED-1 as an -motoneuron trophic factor with long-lasting protective activity.

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