A new pathway in axonal growth: first step to their regeneration after injury

Research Published April 19 2018
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A study led by Bassem Hassan, team leader at ICM, and carried out with the VIB Leuven, identified a new pathway enhancing axonal growth during development and after injury in drosophila. Results just came out in Frontiers in Cellular Neuroscience.

Central nervous system (CNS) injury, such as spine lesion or neurodegeneration, have long-term consequences with more or less severe disabilities. The principal issue is that severed connections fail to regenerate after trauma. Understanding the fundamental mechanisms of axons development and growth is a major challenge and a first step in the hope of restoring lost functions.

A study conducted by Bassem Hassan addressed this problem by performing a genetic screen in Drosophila to identify genes involved in axonal growth after injury. The Drosophila central nervous system shows strong similarities to mammals in all the key morphological, genetic and molecular aspects. Thus it is a relevant and powerful model to study CNS axonal regeneration.

Researchers studied more than 300 genes and identified 13 promoting axonal growth in CNS neurons. Then they tested the effects of those genes in Drosophila with CNS injury. 3 of them were strongly involved as axonal growth regulators: Dscam1, Faf and JNK.

To understand how these regulators are actually involved at the molecular and cellular levels, the scientists, led by frst author Dr. Marta Koch, carried out further analysis and found that the 3 genes actually interacted with each other in a novel axonal growth and regeneration signaling pathway. In this pathway, Fat facets (Faf) promotes axonal regrowth after injury via the Down syndrome cell adhesion molecule (Dscam1) and JNK signaling. Previous data suggest that this mechanism is conserved in mammals. These results open novel perspectives in the study of axonal development and regeneration after injury.

Reference : A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury. Koch M, Nicolas M, Zschaetzsch M, de Geest N, Claeys A, Yan J, Morgan MJ, Erfurth ML, Holt M, Schmucker D, Hassan BA. Front Cell Neurosci. 2018 Feb 8