title: Reciprocal interactions between neurons and glia are required for Drosophila peripheral nervous system development.
abstract: A major developmental role of peripheral glia is to mediate sensory axon guidance; however, it is not known whether sensory neurons influence peripheral glial development. To determine whether glia and neurons reciprocally interact during embryonic development, we ablated each cell type by overexpressing the apoptosis gene, grim, and observed the effects on peripheral nervous system (PNS) development. When neurons are ablated, glial defects occur as a secondary effect, and vice versa. Therefore glia and neurons are codependent during embryogenesis. To further explore glial-neuronal interactions, we genetically disrupted glial migration or differentiation and observed the secondary effects on sensory neuron development. Glial migration and ensheathment of PNS axons was blocked by overexpression of activated Rho GTPase, a regulator of actin dynamics. Here, sensory axons extended to the CNS without exhibiting gross pathfinding errors. In contrast, disrupting differentiation by expression of dominant-negative Ras GTPase in glia resulted in major sensory axon pathfinding errors, similar to those seen in glial ablations. Glial overexpression of transgenic components of the epidermal growth factor receptor (EGFR) signaling pathway yielded similar sensory neuron defects and also downregulated the expression of the glial marker Neuroglian. Mutant analysis also suggested that the EGFR ligands Spitz and Vein play roles in peripheral glial development. The observations support a model in which glia express genes necessary for sensory neuron development, and these genes are potentially under the control of the EGFR/Ras signaling pathway.
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, Canada V6T 1Z4.
authors.forename: Katharine J
authors.initials: KJ
authors.lastname: Sepp
authors.forename: Vanessa J
authors.initials: VJ
authors.lastname: Auld
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D019521:Body Patterning; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004815:Epidermal Growth Factor; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000378:metabolism; D020880:Neuregulins / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology*; D017933:Peripheral Nervous System / Q000166:cytology / Q000196:embryology*; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D008565:Membrane Proteins; D020880:Neuregulins; C061745:Nrg protein, Drosophila; C076026:spi protein, Drosophila; C102104:vn protein, Drosophila; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D018631:ras Proteins; D020741:rho GTP-Binding Proteins