RT Journal Article
SR Electronic
T1 Homeoprotein ENGRAILED-1 promotes motoneuron survival and motor functions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 734020
DO 10.1101/734020
A1 Stephanie E. Vargas Abonce
A1 Mélanie Lebœuf
A1 Kenneth L. Moya
A1 Alain Prochiantz
YR 2020
UL http://biorxiv.org/content/early/2020/03/20/734020.abstract
AB 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 α-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 α-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 α-motoneurons and is rescued following ENGRAILED-1 injection. These results identify ENGRAILED-1 as an α-motoneuron trophic factor with long-lasting protective activity.