Next Article in Journal
Editorial of the Special Issue: Signaling Molecules and Signal Transduction in Cells
Previous Article in Journal
Application of Monoclonal Antibody G250 Recognizing Carbonic Anhydrase IX in Renal Cell Carcinoma
Int. J. Mol. Sci. 2013, 14(6), 11424-11437; doi:10.3390/ijms140611424
Article

Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

1
, 1
, 2
, 3
, 2
, 3
, 1
 and 1,*
1 Cellular Neurobiology Group, IUNICS and Department of Biology, University of the Balearic Islands, Palma de Mallorca 07122, Spain 2 Neuronal Signaling Unit, Department of Basic Medical Sciences, University of Lleida-IRBLLEIDA, Lleida 25198, Spain 3 Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, Seville 41009, Spain
* Author to whom correspondence should be addressed.
Received: 19 April 2013 / Revised: 2 May 2013 / Accepted: 17 May 2013 / Published: 29 May 2013
(This article belongs to the Section Molecular Pathology)
View Full-Text   |   Download PDF [3895 KB, uploaded 19 June 2014]   |   Browse Figures

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.
Keywords: SMA; Notch; NICD; Jagged1; Delta1; Neurogenin 3; astrocyte; motoneuron SMA; Notch; NICD; Jagged1; Delta1; Neurogenin 3; astrocyte; motoneuron
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Export to BibTeX |
EndNote


MDPI and ACS Style

Caraballo-Miralles, V.; Cardona-Rossinyol, A.; Garcera, A.; Torres-Benito, L.; Soler, R.M.; Tabares, L.; Lladó, J.; Olmos, G. Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy. Int. J. Mol. Sci. 2013, 14, 11424-11437.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert