Predetermined embryonic glial cells form the distinct glial sheaths of theDrosophilaperipheral nervous system

Abstract

One of the numerous functions of glial cells in Drosophila is the ensheathment of neurons to isolate them from the potassium-rich haemolymph, thereby establishing the blood-brain barrier. Peripheral nerves of flies are surrounded by three distinct glial cell types. Although all embryonic peripheral glia (ePG) have been identified on a single-cell level, their contribution to the three glial sheaths is not known. We used the Flybow system to label and identify each individual ePG in the living embryo and followed them into third instar larva. We demonstrate that all ePG persist until the end of larval development and some even to adulthood. We uncover the origin of all three glial sheaths and describe the larval differentiation of each peripheral glial cell in detail. Interestingly, just one ePG (ePG2) exhibits mitotic activity during larval stages, giving rise to up to 30 glial cells along a single peripheral nerve tract forming the outermost perineurial layer. The unique mitotic ability of ePG2 and the layer affiliation of additional cells were confirmed by in vivo ablation experiments and layer-specific block of cell cycle progression. The number of cells generated by this glial progenitor and hence the control of perineurial hyperplasia correlate with the length of the abdominal nerves. By contrast, the wrapping and subperineurial glia layers show enormous hypertrophy in response to larval growth. This characterisation of the embryonic origin and development of each glial sheath will facilitate functional studies, as they can now be addressed distinctively and genetically manipulated in the embryo.

Axonal wrapping in theDrosophilaPNS is controlled by glia-derived neuregulin homolog Vein

“…The relatively constant number of wrapping and subperineurial glial cells in each abdominal nerve in relation to the enormous growth of the larva points towards an extreme hypertrophic growth and differentiation potential of these cells (von Hilchen et al, 2013; and see Fig. 1).…”

“…The black lines indicate the distances from the vnc at which the sections were taken for ultrastructural analysis. The nerve extension region is defined as the part of the axon from the vnc to the muscle field area (von Hilchen et al, 2013). DLN, dorsal longitudinal nerve; ISN, intersegmental nerve; SN, segmental nerve; TN, transversal nerve.…”

“…In the third larval instar stage, the wrapping glial cells have engulfed all axons but never form multiple membrane wraps as observed in the vertebrate myelin (Stork et al, 2008). The lineage and identity of all peripheral glial cells found in the larval PNS has been recently described (von Hilchen et al, 2013). Along every abdominal nerve, only three to four wrapping glial cells are found.…”

“…The SPG is also generated during early embryogenesis. These cells do not divide once they are born and persist until adult stages (Awasaki et al, 2008;Stork et al, 2008;Unhavaithaya and OrrWeaver, 2012;von Hilchen et al, 2013). The SPG forms the bloodbrain barrier by establishing intensive cell-cell contacts characterized by pleated septate junctions ( pSJ).…”

N-cadherin negatively regulates collective Drosophila glial migration via actin cytoskeleton remodeling

“…Tumor glial cells move through the nerve tissue, leading to formation of glioma, the most aggressive form of cancer in the nervous system (Cayre et al, 2009). In addition, glia of the peripheral nervous system (PNS), such as vertebrate perineurium and Schwann cells (Klämbt, 2009), as well as embryonic and pupal Drosophila and Manduca glia, move as collectives to reach their final destination (Cafferty and Auld, 2007;Klämbt, 2009;Koussa et al, 2010;Silies and Klambt, 2010a;von Hilchen et al, 2008;von Hilchen et al, 2013). This makes glia a valuable tool to analyze the role of cadherins in cell migration in the nervous system.…”