Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling

Anindya Sen, Takakazu Yokokura, Mark W. Kankel, Douglas N. Dimlich, Jan Manent, Subhabrata Sanyal, Spyros Artavanis-Tsakonas

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33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)481-495
Number of pages15
JournalJournal of Cell Biology
Volume192
Issue number3
DOIs
Publication statusPublished - 7 Feb 2011
Externally publishedYes

Cite this

Sen, A., Yokokura, T., Kankel, M. W., Dimlich, D. N., Manent, J., Sanyal, S., & Artavanis-Tsakonas, S. (2011). Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling. Journal of Cell Biology, 192(3), 481-495. https://doi.org/10.1083/jcb.201004016