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Understanding the molecular mechanisms underlying glia-glia communication in the Drosophila peripheral nerve

University of British Columbia

Development and maintenance of the peripheral nervous system (PNS) relies on glial cells that insulate and protect axons. In invertebrates, wrapping glia isolate axons into separate bundles similar to non-myelinating Schwann cells (NMSCs) in vertebrate Remak bundles. The mechanisms by which NMSCs communicate with each other remains unknown. In this thesis, we focused on identifying and characterizing proteins required for glia-glia communication in non-myelinating classes of glia using the Drosophila peripheral nerve as our model. We show that Innexin1 (Inx1) and Innexin2 (Inx2) based gap junctions (GJs) exist between two peripheral glial layers, the subperineurial glia (SPG) and wrapping glia (WG). WG survival is dependent on its communication with the SPG and is mediated by a channel rather than adhesive function of Inx2. Inx2 GJs mediate calcium pulses exclusively in the SPG and WG survival is not dependent on Ca²⁺ and inositol 1,4,5-trisphosphate (IP3). Therefore, we find that GJs mediate glia-glia communication to ensure the survival of WG through an unknown mechanism. We next tested the role of scaffolding complexes in mediating glia-glia communication and screened for the role of the PSD95-Dlg-ZO1 (PDZ) family of proteins. We identified a role for Dlg5, a membrane-associated guanyl kinase protein, in peripheral glia. Loss of Dlg5 results in glial disruptions, including loss of septate junction formation and axonal ensheathment. Dlg5 has multiple roles identified in other systems including trafficking of cadherins. However, in glia the loss of Dlg5 did not affect cadherin localization to spot adherens junctions (SAJs). Therefore, we find that Dlg5 plays a novel role in peripheral glial development. SAJs were previously identified in the Drosophila peripheral glia, but the composition and function of this complex had not been characterized. We find that classical cadherins associate with catenins in the peripheral nerve, and loss of DE-Cad but not DN-Cad leads to disruptions in glial morphology. However, loss of DE-Cad does not affect SAJ assembly, suggesting a redundancy with DN-Cad in peripheral glia. Taken together this thesis provides novel insights and proposed models by which glia communicate in the PNS and will help direct future work in NMSCs in all animals.

Text

2018-03-28

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/64981

Zoology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/