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Perineurial glia regulate morphology of the Drosophila nervous system

University of British Columbia

The nervous system is surrounded by neural lamella composed of large glycoproteins including perlecan, collagen and laminin, which bind to underlying perineurial glial cells. The function of perineurial glia and their interaction with the neural lamella is just beginning to be elucidated. Previous studies have demonstrated that integrin is critical for glial wrapping in both vertebrates and Drosophila. Therefore, we have focused on perineurial glia and the role of laminin, an integrin ligand, and basigin, a transmembrane protein known to interact with integrin. Laminin is a heterotrimer composed of an alpha (LanA or Wb), beta (LanB1) and gamma (LanB2) subunit and we demonstrate that LanB2 loss in glia results in accumulation of LanB1 leading to distended ER, ER stress and glial swelling in addition to decreased larval locomotion and lethality. Loss of LanB2 in wrapping glia affected glial ensheathment of axons but surprisingly not larval locomotion. We found that Tango1, a protein thought to exclusively mediate collagen secretion, is also important for laminin secretion in glia via a collagen-independent mechanism. We conclude that it is the loss of one laminin subunit that leads to deleterious consequences through the accumulation of the remaining subunits. Basigin is a highly conserved transmembrane protein involved in cancer metastasis, however its developmental roles are just beginning to be elucidated. We show that basigin is specifically expressed in perineurial glia where it is present in a complex with integrin. Basigin knockdown resulted in a shortened ventral nerve cord, ruffles in the peripheral nerves as well as a collapsed actin cytoskeleton and a redistribution of myosin motors in perineurial glia. We examined the domains within basigin that are required for association with integrin and also examined the effect of basigin knockdown on integrin-associated proteins. Together, the results in this thesis highlight the role of perineurial glia in secreting laminin, facilitating larval locomotion and regulating both central and peripheral nervous system morphology in Drosophila. Due to the conserved structure and function of glia between vertebrates and Drosophila, these results will help direct future research on how perineurial glia regulate nervous system development.

Text

2016-04-15

Attribution-NonCommercial 4.0 International

http://hdl.handle.net/2429/57608

Zoology

University of British Columbia

UBCV

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