Homeoprotein ENGRAILED-1 promotes motoneuron survival and motor functions

Abstract

Conflict of Interest Statement: AP and KLM are on several patents for HP therapeutic use and co-founders of BrainEver. SEVA and ML are BrainEver post-doctorant and doctorant, respectively.Funding sources: MemoLife Labex PhD fellowship to SEVA, Association Nationale de la Recherche et de la Technologie (Cifre/ANRT n° 2017/0488) to ML, BrainEver, HomeoSign ERC -2013-AdG n°339379. ABSTRACTMotoneuron 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.

Announcing the winners of our COVID‐19 Creative Communication Competition

“…The main theme of Stephanie's thesis was the exploration of the effect of the homeoprotein EN1 in motor neuron physiology and survival. Her PhD work led to two main papers; the one that is relevant to her comic is in a preprint format in bioRxiv [2]. The artist of the comic, Danae Solis, is an undergraduate student.…”