Banerjee Chatterjee, P.; Demarque, M.; Benchetrit, A.; Champelovier, D.; Froc, C.; Paul, M.; Wiggett, H.; Jenett, A.; Levraud, J.-P.

Zebrafish possess remarkable regeneration abilities, including the capacity to repair their central nervous system (CNS). Leveraging the optical accessibility of the zebrafish brain, we investigated the mechanisms underlying meningeal repair following laser-induced brain injuries to the optic tectum. In previous work, using live imaging of laser-induced surface injuries to the optic tectum in juvenile zebrafish, we identified a population of flat PDGFR{beta}+ cells that rapidly migrate to the wound site and contribute to meningeal repair. Here, using pharmacological inhibition or genetic perturbation of PDGFR{beta}, we show that recruitment of these PDGFR{beta}+ meningeal cells is strongly dependent on PDGFR{beta} signaling, unlike recruitment of PDGFR{beta}+ pericytes deeper in the wound. Furthermore, PDGFR{beta} inhibition diminishes neurite regrowth and macrophage recruitment. Using photoconversion assays, we traced the origin of PDGFR{beta}+ meningeal cells that migrated to the wound in response to injury, in the midbrain-forebrain and midbrain-hindbrain sulci. Our findings highlight pivotal role of PDGFR{beta} in orchestrating meningeal repair and reveal novel cellular dynamics during CNS regeneration. These results provide insights into potential therapeutic strategies for enhancing brain repair and mitigating fibrosis in mammals, where meningeal scarring remains a barrier to CNS regeneration.