When central nervous system (CNS) neurons are damaged or lost, e.g. in spinal cord injury, glia over-proliferate leading to spontaneous remyelination and homeostasis maintenance, known as the glial repair response. This repair response is limited, but it reveals a tendency of the CNS to repair itself.
This is also manifested during normal development as neuronal and glial populations adjust cell number and axonal patterns to maintain structural CNS robustness. Upon spinal cord injury in mice, transplantation of non-myelinating ensheathing glia to the site of injury is sufficient to repair axonal trajectories and neuronal function. Thus, restoring glial populations may be both necessary and sufficient to promote CNS repair.
It is thus a great challenge to harness the glial repair response to implement repair. Little is known of what genes control glial precursor proliferation and differentiation. In mammals, Notch1 maintains glial precursors proliferative and Tumor Necrosis Factor provokes proliferation of glial precursors upon injury.
However, finding out whether a common genetic network underlies these observations, and whether they have any relevance for repair in vivo, is extremely challenging in vertebrates. Gene function can be tested in glia in vivo, in time-lapse and with single cell resolution using Drosophila as a model organism. Findings from Drosophila can then be tested in human glial precursors.
The applicant has discovered a glial repair-response in Drosophila adults, which depends on the gene eiger, a TNF-superfamily member. The host discovered a glial repair-response in the Drosophila embryo that requires the genes Notch and prospero, which control cell cycle gene expression and maintain glial precursors immature.
The aim is to test here whether a universal gene network linking the functions of Notch, Prospero and Eiger/TNF controls the glial repair-response and whether this gene network influences the recovery of axons upon injury in vivo.
Fields of science
- medical and health sciencesbasic medicinephysiologyhomeostasis
- natural sciencesphysical sciencesopticsmicroscopyconfocal microscopy
- social sciencesother social sciencessocial sciences interdisciplinarysustainable development
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesclinical medicinetransplantation
- natural sciencesbiological sciencesneurobiology
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