The mammalian central nervous system (CNS) exhibits limited regenerative capacity, and the mechanisms that mediate regeneration are not fully understood. Here we present a novel experimental design to damage the CNS using a contusion injury paradigm. The design of this novel protocol allows the study of long term and short term cellular responses including the CNS and the immune system, and the implications for functional recovery. We demonstrate for the first time that adult Drosophila undergoes spontaneous functional recovery following injury. This crush injury leads to an intermediate level of functional recovery after damage, which is ideal to screen for genes that facilitate or prevent the regeneration process. Here we validate this model and analyze the immune responses of glial cells as a central regulator of functional regeneration. Additionally, we demonstrate that glia and macrophages contribute to functional regeneration through mechanisms involving the c-Jun N-terminal kinase (JNK) pathway and Draper, characteristic of other neural injury paradigms. We show that macrophages are recruited to the injury site and are required for recovery. Further, we show that Grindelwald and Draper in glial cells mediate JNK activation, and draper expression in turn, is dependent on JNK activation. Finally, we link neuron-glia communication and the requirement of neuronal vesicular transport for JNK pathway regulation and functional recovery.

This content is only available via PDF.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Article PDF first page preview

Article PDF first page preview