Biology subjects

Matzat, T.

Publications and source records attributed to Matzat, T..

3 recordsLinked to original sources

bioRxiv2022

Dlg5 and Cadherins are key to peripheral glia integrity

Glial cells in the peripheral nerve wrap axons to insulate them and ensure efficient conduction of neuronal signals. In the myelin sheath, it is proposed that the autotypic tight junctions and adherens junctions form glia-glia complexes that stabilize the glia sheath in myelinating glia. Yet the role of adhesion junctions in non-myelinating glia of vertebrates or invertebrates has not been clearly established. Many components of adhering junctions contain PDZ (PSD-95, Dlg, ZO1) domains or are recruited to these junctions by PDZ binding motifs. To test for the role of PDZ domain proteins in glial sheath formation, we carried out an RNAi screen using Drosophila melanogaster to knockdown each of the 66 predicted PDZ domain proteins in the peripheral glia. We identified six PDZ genes with potential roles in glial morphology, and further investigated Discs-large 5 (Dlg5), a scaffolding protein with no previously known function in glia. Knockdown of Dlg5 disrupts subperineurial glia (SPG) morphology, including gaps in the membrane that coincide with disruption of septate junction proteins. To further our investigation of Dlg5, we focused on cadherins and found both N-Cadherin and E-Cadherin are expressed throughout peripheral glia. Knockdown of E-Cadherin phenocopied the loss of Dlg5 leading to gaps in the SPG and septate junctions while only simultaneous loss of both N-Cadherins (NCad, and CadN2) had the same effect. The loss of all three Cadherins enhanced these phenotypes as did loss of Dlg5 when paired with cadherin knockdown. This leads to a model where Dlg5 plays a role in conjunction with cadherins in glial membrane stabilization and septate junction formation in the subperineurial glia.

neuroscience↗

bioRxiv2022

Innexin-mediated adhesion between glia is required for axon ensheathment in the peripheral nervous system

Glia are essential to protecting and enabling nervous system function and a key glial function is the formation of the glial sheath around peripheral axons. Each peripheral nerve in the Drosophila larva is ensheathed by three glial layers, which structurally support and insulate the peripheral axons. How peripheral glia communicate with each other and between layers is not well established and we investigated the role of Innexins in mediating glial function in the Drosophila periphery. Of the eight Drosophila Innexins, we found two (Inx1 and Inx2) are important for peripheral glia development. In particular loss of Inx1 and Inx2 resulted in defects in the wrapping glia leading to disruption of the glia wrap. Of interest loss of Inx2 in the subperineurial glia also resulted in defects in the neighbouring wrapping glia. Inx plaques were observed between the subperineurial glia and the wrapping glia suggesting that gap junctions link these two glial cell types. We found Inx2 is key to Ca+2 pulses in the peripheral subperineurial glia but not in the wrapping glia, and we found no evidence of gap junction communication between subperineurial and wrapping glia. Rather we have clear evidence that Inx2 plays an adhesive and channel-independent role between the subperineurial and wrapping glia to ensure the integrity of the glial wrap.

neuroscience↗

bioRxiv2019

Matrix metalloproteinase 1 modulates invasive behavior of tracheal branches during ingression into Drosophila flight muscles

Tubular networks like the vasculature extend branches throughout the bodies of animals, but how developing vessels interact with and invade tissues is not well understood. We investigated the underlying mechanisms using the developing tracheal tube network of Drosophila indirect flight muscles (IFMs) as a model. Live imaging revealed that tracheal sprouts invade IFMs directionally with growth-cone-like structures at branch tips. Ramification inside IFMs proceeds until tracheal branches fill the myotube. However, individual tracheal cells occupy largely separate territories, possibly mediated by cell-cell repulsion. Matrix metalloproteinase 1 (MMP1) is required in tracheal cells for normal invasion speed and for the dynamic organization of growth-cone-like branch tips. MMP1 remodels the Collagen IV-containing matrix around branch tips and promotes degradation of Branchless FGF in cultured cells. Thus, tracheal-derived MMP1 may play dual roles in sustaining branch invasion by modulating ECM properties as well as by shaping the distribution of the FGF chemoattractant.

cell biology↗