Control of Drosophila perineurial glial growth by interacting neurotransmitter-mediated signaling pathways

Drosophila peripheral nerves, similar structurally to the peripheral nerves of mammals, comprise a layer of axons and inner glia, surrounded by an out er perineurial glial layer. Although it is well established that intercellu lar communication occurs among cells within peripheral nerves, the signalin g pathways used and the effects of this signaling on nerve structure and fu nction remain incompletely understood. Here we demonstrate with genetic met hods that the Drosophila peripheral nerve is a favorable system for the stu dy of intercellular signaling. We show that growth of the perineurial glia is controlled by interactions among five genes: ine, which encodes a putati ve neurotransmitter transporter; eag, which encodes a potassium channel; pu sh, which encodes a large, Zn(2+-)finger-containing protein; amn, which enc odes a putative neuropeptide related to the pituitary adenylate cyclase act ivator peptide; and NF1, the Drosophila ortholog of the human gene responsi ble for type 1 neurofibromatosis. In other Drosophila systems, push and NF1 are required for signaling pathways mediated by Amn or the pituitary adeny late cyclase activator peptide. Our results support a model in which the Am n neuropeptide, acting through Push and NF1, inhibits perineurial glial gro wth, whereas the substrate neurotransmitter of Ine promotes perineurial gli al growth. Defective intercellular signaling within peripheral nerves might underlie the formation of neurofibromas, the hallmark of neurofibromatosis .