Kon-Tiki gene network for CNS regeneration (KON-TIKIGENET)
Kon-Tiki gene network for CNS regeneration
Start date: Mar 1, 2014,
End date: Jul 30, 2016
Regeneration after injury occurs in many animals, revealing that cellular and molecular mechanisms regulate normal organ structure, size and shape. The human central nervous system (CNS) does not regenerate upon damage and as a consequence stroke, spinal cord injury, multiple sclerosis and neurodegenerative diseases result in permanent disability. NG2 cells are repair cells in mammals that respond to CNS injury by proliferating to produce ensheathing glia and trophic factors that favor axonal growth. A promising approach to CNS repair is to transplant NG2+ glial progenitors or stem cells to the site of damage. However, it is unknown how to control the proliferation and differentiation of transplanted cells, to ensure repair and prevent unwanted outcomes (e.g. cancer).The glial regenerative response is found across the animals, from cockroaches and flies, to fish and mice, implying that there is an underlying genetic mechanism that has been evolutionarily conserved. Drosophila is a powerful model organism to discover gene networks and test gene function in vivo, and has recurrently led to discoveries relevant to human health. The Host laboratory recently discovered a gene network in Drosophila that can be manipulated in glia to promote CNS repair and the Researcher extended the injury method to enable the assessment of locomotion recovery. There is a Drosophila homologue of NG2 called kon-tiki (kon), but whether it has functions in repair and whether it is functionally linked to the regnerative gene network is unknown.The aim is to investigate the functions of kon in the glial regenerative response in Drosophila. The objectives are: (1) To characterise the cells expressing kon, test whether Kon is linked to Pros and/or Notch, and investigate its functions in the normal CNS. (2) To investigate whether Kon influences the glial and axonal regenerative responses to CNS injury. (3) To test if candidate genes expressed in neurons interact with glial kon.
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