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Reduced levels of survival motor neuron protein leads to aberrant motoneuron growth in a Xenopus model of muscular atrophy

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Abstract

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by motor neuron loss and skeletal muscle atrophy. The loss of function of the smn1 gene, the main supplier of survival motor neuron protein (SMN) protein in human, leads to reduced levels of SMN and eventually to SMA. Here, we ask if the amphibian Xenopus tropicalis can be a good model system to study SMA. Inhibition of the production of SMN using antisense morpholinos leads to caudal muscular atrophy in tadpoles. Of note, early developmental patterning of muscles and motor neurons is unaffected in this system as well as acetylcholine receptors clustering. Muscular atrophy seems to rather result from aberrant pathfinding and growth arrest and/or shortening of motor axons. This event occurs in the absence of neuronal cell bodies apoptosis, a process comparable to that of amyotrophic lateral sclerosis. Xenopus tropicalis is revealed as a complementary animal model for the study of SMA.

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Acknowledgement

The authors wish to thank Christophe de Medeiros for animal care. We express our gratitude to Dr. Nacira Tabti for very stimulating discussions. The support of Gregory Lemkine from Watchfrog is gratefully acknowledged. This work was funded by grants from Genopole, the Conseil General de l’Essonne (ASTRE T-REX), CNRS, and under the auspice of the X-OMICS European coordinated action from FP6.

Author information

Correspondence to Nicolas Pollet.

Additional information

Qods Ymlahi-Ouazzani and Odile Bronchain contributed equally to the work

Electronic supplementary materials

Below is the link to the electronic supplementary material.

smn loss of function induces a paralysis in X. tropicalis tadpoles. (MOV 3292 kb)

ESM Fig. 1

X. laevis smn mRNA rescues the smn morphant phenotype in X. tropicalis. a Lateral views of MoSMNd (30 ng)-injected tail bud embryos; b lateral views of MoSMNd and X. laevis smn mRNA (1 ng) co-injected tail bud embryos.

ESM Fig. 2

Patterning of muscle and motoneuron axons is not affected in smn morphant embryos. Lateral views, dorsal to the top, anterior to the right, of either wild-type (left column) or morphant (right column, using 15 ng of MoSMNd) tail bud stage embryos after whole-mount in situ hybridization using probes indicated on the left.

ESM Fig. 3

Patterns of apoptosis are not affected in smn morphant embryos. Transverse sections of tadpoles at the level of the trunk (stage 35) or tail (stage 45) are shown, dorsal to the top. Apoptosis was detected by a TUNEL staining (in green), and cells were counterstained using hoechst (violet). sc spinal cord, no notochord, so somites. No differences were observed in staining between control and morphant tadpoles.

Supplementary Movie 1

smn loss of function induces a paralysis in X. tropicalis tadpoles. (MOV 3292 kb)

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Ymlahi-Ouazzani, Q., J. Bronchain, O., Paillard, E. et al. Reduced levels of survival motor neuron protein leads to aberrant motoneuron growth in a Xenopus model of muscular atrophy. Neurogenetics 11, 27–40 (2010) doi:10.1007/s10048-009-0200-6

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Keywords

  • Spinal muscular atrophy
  • Xenopus tropicalis
  • Survival motor neuron
  • SMN
  • SMA