Dystroglycan mediates polarized deposition of laminin and axon ensheathment by wrapping glia.

Abstract

The Drosophila peripheral nerve contains multiple layers of glial cells and an overlying extracellular matrix, which together support neuronal survival and function. The innermost glial layer, the wrapping glia (WG), ensheathes axons and facilitates action potential conduction. Recent work has identified involvement of laminin, a heterotrimeric extracellular matrix protein complex in WG development. However, the localization and function of laminin in the WG remains poorly understood. Here, we found that the α subunit, Laminin A (LanA), is dynamically expressed by WG, and loss of LanA results in a reduction in WG-axon contact. The deposition of LanA by WG is concentrated between WG and axons and is deposited preferentially around motor axons versus sensory axons. We identified Crag, a GDP-GTP exchange protein, as a factor that controls LanA deposition. We found that Dystroglycan also controls LanA deposition by the WG, and that both Dystroglycan and Dystrophin are present and necessary for WG ensheathment of axons. Thus, WG contain the highly conserved Dystroglycan/Dystrophin complex, which not only associates with deposited laminin but is necessary for the polarized deposition of laminin and the correct ensheathment of peripheral nerve axons.