TY - JOUR
T1 - Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling
AU - Sen, Anindya
AU - Yokokura, Takakazu
AU - Kankel, Mark W.
AU - Dimlich, Douglas N.
AU - Manent, Jan
AU - Sanyal, Subhabrata
AU - Artavanis-Tsakonas, Spyros
PY - 2011/2/7
Y1 - 2011/2/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79551706478&partnerID=8YFLogxK
U2 - 10.1083/jcb.201004016
DO - 10.1083/jcb.201004016
M3 - Article
C2 - 21300852
AN - SCOPUS:79551706478
SN - 0021-9525
VL - 192
SP - 481
EP - 495
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 3
ER -