title: Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling.
abstract: Spinal muscular atrophy (SMA), a devastating neurodegenerative disorder characterized by motor neuron loss and muscle atrophy, has been linked to mutations in the Survival Motor Neuron (SMN) gene. Based on an SMA model we developed in Drosophila, which displays features that are analogous to the human pathology and vertebrate SMA models, we functionally linked the fibroblast growth factor (FGF) signaling pathway to the Drosophila homologue of SMN, Smn. Here, we characterize this relationship and demonstrate that Smn activity regulates the expression of FGF signaling components and thus FGF signaling. Furthermore, we show that alterations in FGF signaling activity are able to modify the neuromuscular junction defects caused by loss of Smn function and that muscle-specific activation of FGF is sufficient to rescue Smn-associated abnormalities.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Anindya
authors.initials: A
authors.lastname: Sen
authors.forename: Takakazu
authors.initials: T
authors.lastname: Yokokura
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kankel
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Dimlich
authors.forename: Jan
authors.initials: J
authors.lastname: Manent
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Sanyal
authors.forename: Spyros
authors.initials: S
authors.lastname: Artavanis-Tsakonas
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; C542563:Smn protein, Drosophila; D005346:Fibroblast Growth Factors