Insulin-driven neurogenic response of glia to central nervous system injury in Drosophila

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Connolly, Elizabeth ORCID: https://orcid.org/0000-0002-5716-8889 (2021). Insulin-driven neurogenic response of glia to central nervous system injury in Drosophila. University of Birmingham. Ph.D.

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Abstract

The human central nervous system (CNS) cannot regenerate upon injury, however those of some animals can. Understanding the mechanisms underlying regenerative responses could help promote regeneration in humans. Regenerative neurogenesis in animals originates from glial cells, suggesting that glial cells might have a fundamental neurogenic potential. The glial protein Neuron-glia antigen-2 (NG2) could be involved, but the molecular mechanism underlying the neurogenic potential of glia is not known.

Using Drosophila melanogaster, I investigated the function of Islet antigen-2 (Ia-2). Ia-2 interacts with the homologue of NG2, kon-tiki (kon), and modulates the secretion of insulin from neurons. Both ia-2 over-expression and loss of function induced ectopic expression of the neural stem cell marker deadpan (dpn) in the larval CNS. Injury to the larval CNS also induced ectopic Dpn cells. Genetic epistasis analysis and lineage tracing showed that Ia-2, Dilp-6 and InR induce glial proliferation and ectopic Dpn expression from glia. Ectopic Dpn cells could divide and limited de novo neurogenesis was traced back to glial cells.

These findings suggest that a neuron-glia relay driven by Ia-2 and Dilp-6 could regenerate glial populations and reprogramme some glia into neural stem cells, thus restoring the two cell populations required for CNS regeneration.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):