title: Notch signaling pathway is activated in motoneurons of spinal muscular atrophy.
abstract: Spinal muscular atrophy (SMA) is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN) protein that affects alpha motoneurons in the spinal cord. Notch signaling is a cell-cell communication system well known as a master regulator of neural development, but also with important roles in the adult central nervous system. Aberrant Notch function is associated with several developmental neurological disorders; however, the potential implication of the Notch pathway in SMA pathogenesis has not been studied yet. We report here that SMN deficiency, induced in the astroglioma cell line U87MG after lentiviral transduction with a shSMN construct, was associated with an increase in the expression of the main components of Notch signaling pathway, namely its ligands, Jagged1 and Delta1, the Notch receptor and its active intracellular form (NICD). In the SMNΔ7 mouse model of SMA we also found increased astrocyte processes positive for Jagged1 and Delta1 in intimate contact with lumbar spinal cord motoneurons. In these motoneurons an increased Notch signaling was found, as denoted by increased NICD levels and reduced expression of the proneural gene neurogenin 3, whose transcription is negatively regulated by Notch. Together, these findings may be relevant to understand some pathologic attributes of SMA motoneurons.
authors.affiliation: Cellular Neurobiology Group, IUNICS and Department of Biology, University of the Balearic Islands, Palma de Mallorca 07122, Spain. gabriel.olmos@uib.es.
authors.forename: Víctor
authors.initials: V
authors.lastname: Caraballo-Miralles
authors.forename: Andrea
authors.initials: A
authors.lastname: Cardona-Rossinyol
authors.forename: Ana
authors.initials: A
authors.lastname: Garcera
authors.forename: Laura
authors.initials: L
authors.lastname: Torres-Benito
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Soler
authors.forename: Lucía
authors.initials: L
authors.lastname: Tabares
authors.forename: Jerònia
authors.initials: J
authors.lastname: Lladó
authors.forename: Gabriel
authors.initials: G
authors.lastname: Olmos
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology*; D009134:Muscular Atrophy, Spinal / Q000378:metabolism* / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D055533:Survival of Motor Neuron 1 Protein / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D055533:Survival of Motor Neuron 1 Protein; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; C407737:Neurog3 protein, mouse; C064045:delta protein