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Author:
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Cardona-Rossinyol, Andrea; Garcera, Ana; Torres-Benito, Laura; Soler i Tatché, Rosa Ma.; Tabares, Lucía; Lladó, Jerònia; Olmos, Gabriel; Caraballo-Miralles, Víctor
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Notes:
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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.
This work was supported by grants from Fundación Genoma España, GENAME to JL, LT and RMS, and from Instituto de Salud Carlos III-Fondo de Investigaciones Sanitarias (PI11/01047) to RMS. AG holds a postdoctoral contract from Genoma España. VC-M and AC-R have been supported by a predoctoral fellowship from “Govern de les Illes Balears, Conselleria d’Educació, Cultura i Universitats” under a program of joint financing with the European Social Fund. |
