title: Plum, an immunoglobulin superfamily protein, regulates axon pruning by facilitating TGF-β signaling.
abstract: Axon pruning during development is essential for proper wiring of the mature nervous system, but its regulation remains poorly understood. We have identified an immunoglobulin superfamily (IgSF) transmembrane protein, Plum, that is cell autonomously required for axon pruning of mushroom body (MB) γ neurons and for ectopic synapse refinement at the developing neuromuscular junction in Drosophila. Plum promotes MB γ neuron axon pruning by regulating the expression of Ecdysone Receptor-B1, a key initiator of axon pruning. Genetic analyses indicate that Plum acts to facilitate signaling of Myoglianin, a glial-derived TGF-β, on MB γ neurons upstream of the type-I TGF-β receptor Baboon. Myoglianin, Baboon, and Ecdysone Receptor-B1 are also required for neuromuscular junction ectopic synapse refinement. Our study highlights both IgSF proteins and TGF-β facilitation as key promoters of developmental axon elimination and demonstrates a mechanistic conservation between MB axon pruning during metamorphosis and the refinement of ectopic larval neuromuscular connections.
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94303, USA.
authors.forename: Xiaomeng M
authors.initials: XM
authors.lastname: Yu
authors.forename: Itai
authors.initials: I
authors.lastname: Gutman
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mosca
authors.forename: Tal
authors.initials: T
authors.lastname: Iram
authors.forename: Engin
authors.initials: E
authors.lastname: Ozkan
authors.forename: K Christopher
authors.initials: KC
authors.lastname: Garcia
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.forename: Oren
authors.initials: O
authors.lastname: Schuldiner
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D029404:Activin Receptors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism; D024521:Mushroom Bodies / Q000378:metabolism; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D029721:Drosophila Proteins; D007136:Immunoglobulins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C059253:bw protein, Drosophila; C121965:myo protein, Drosophila; D029404:Activin Receptors; C517157:Babo protein, Drosophila