Dimitris Beis, Vasiliki Tsata and colleagues recently published a manuscript in Developmental Cell

Specific composition of scar tissue permits nerve regrowth after spinal cord injury

Spinal cord injury results in lifelong paralysis because the severed nerve fibres (axons) fail to regrow across the lesion site. Among the mechanisms that limit axon regeneration in the mammalian central nervous system is the formation of scar tissue. The scar forms due to the excessive deposition of extracellular matrix (ECM) molecules by invading fibroblasts and constitutes a hostile environment to axon growth. Unlike mammals, zebrafish can efficiently repair damage to the central nervous system and regrow axons across the lesion site, leading to substantial recovery of swimming function.

However, the difference that causes such opposite fates in man and zebrafish remained largely unknown. Using a panel of novel genetic tools, we identified a population of fibroblasts that – different to mammals – promote axon regeneration in zebrafish. In sharp contrast to their mammalian counterparts, zebrafish fibroblasts secrete a growth-promoting ECM in the spinal lesion site that is deprived of growth-inhibitory matrix molecules.

Our study shows that the composition of the ECM in the scar is a key determinant of regenerative success in zebrafish versus inhibitory scarring in mammals. This insight might help to one day cure spinal cord injuries also in humans, by steering the ECM composition of the scar in the right direction.

A switch in pdgfrb+ cell-derived ECM composition prevents inhibitory scarring and promotes axon regeneration in the zebrafish spinal cord
Tsata V, Möllmert S, Schweitzer C, Kolb J, Möckel C, Böhm B, Rosso G, Lange C, Lesche M, Hammer J, Kesavan G, Beis D, Guck J, Brand M, Wehner D. Dev Cell. 2021 Feb 22;56(4):509-524.e9. doi: 10.1016/j.devcel.2020.12.009. Epub 2021 Jan 6. PMID: 33412105