Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding

doi:10.1083/jcb.200303168

Published 2 September 2003. doi:10.1083/jcb.200303168

This Article

Full Text

Full Text (PDF, 802K)

PPT slides of all figures

Supplemental Material Index

Alert me when this article is cited

Citation Map

Services

Email this article

Similar articles in this journal

Similar articles in PubMed

Alert me to new content in the JCB

Download to citation manager

Citing Articles

Citing Articles via HighWire

Citing Articles via CrossRef

Citing Articles via Google Scholar

Google Scholar

Articles by McWhorter, M. L.

Articles by Beattie, C. E.

Search for Related Content

PubMed

PubMed Citation

Articles by McWhorter, M. L.

Articles by Beattie, C. E.

Pubmed/NCBI databases

Gene	GEO Profiles
HomoloGene	Protein
UniGene

Social Bookmarking

What's this?

© The Rockefeller University Press, 0021-9525/2003/9/919 $5.00
The Journal of Cell Biology, Volume 162, Number 5, 919-932

Article

Knockdown of the survival motor neuron (Smn) protein in zebrafish causes defects in motor axon outgrowth and pathfinding

Michelle L. McWhorter¹^,2, Umrao R. Monani³, Arthur H.M. Burghes²^,3^,4^,5 and Christine E. Beattie¹^,2^,6

¹ Center for Molecular Neurobiology, Cellular, and Developmental Biology Program
² Molecular, Cellular, and Developmental Biology Program
³ Department of Neurology, The Ohio State University, Columbus, OH 43210
⁴ Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210
⁵ Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210
⁶ Department of Neuroscience, The Ohio State University, Columbus, OH 43210

Address correspondence to Christine E. Beattie, Center for Molecular Neurobiology, The Ohio State University, 115 Rightmire Hall, 1060 Carmack Road, Columbus, OH 43210. Tel.: (614) 292-5113. Fax: (614) 292-5379. email: beattie.24{at}osu.edu

Spinal muscular atrophy (SMA) is an autosomal recessive disordercharacterized by a loss of ${alpha}$ motoneurons in the spinal cord.SMA is caused by low levels of the ubiquitously expressed survivalmotor neuron (Smn) protein. As it is unclear how low levelsof Smn specifically affect motoneurons, we have modeled SMAin zebrafish, a vertebrate model organism with well-characterizedmotoneuron development. Using antisense morpholinos to reduceSmn levels throughout the entire embryo, we found motor axon–specificpathfinding defects. Reduction of Smn in individual motoneuronsrevealed that smn is acting cell autonomously. These resultsshow for the first time, in vivo, that Smn functions in motoraxon development and suggest that these early developmentaldefects may lead to subsequent motoneuron loss.

Key Words: SMA; SMN; motoneurons; zebrafish; morpholino

The online version of this article includes supplemental material.

Abbreviations used in this paper: AChR, acetylcholine receptor;CaP, caudal primary; MO, morpholino oligonucleotide; SMA, spinalmuscular atrophy; SMN, survival motor neuron; VeLD, ventrallongitudinal descending.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Butchbach, M. E.R., Singh, J., Thorsteinsdottir, M., Saieva, L., Slominski, E., Thurmond, J., Andresson, T., Zhang, J., Edwards, J. D., Simard, L. R., Pellizzoni, L., Jarecki, J., Burghes, A. H.M., Gurney, M. E. (2009). Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy. Hum Mol Genet 0: ddp510v2-ddp510 [Abstract] [Full Text]
Murray, L. M., Lee, S., Baumer, D., Parson, S. H., Talbot, K., Gillingwater, T. H. (2009). Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy. Hum Mol Genet 0: ddp506v2-ddp506 [Abstract] [Full Text]
Mattis, V. B., Ebert, A. D., Fosso, M. Y., Chang, C.-W., Lorson, C. L. (2009). Delivery of a read-through inducing compound, TC007, lessens the severity of a spinal muscular atrophy animal model. Hum Mol Genet 18: 3906-3913 [Abstract] [Full Text]
Garbes, L., Riessland, M., Holker, I., Heller, R., Hauke, J., Trankle, C., Coras, R., Blumcke, I., Hahnen, E., Wirth, B. (2009). LBH589 induces up to 10-fold SMN protein levels by several independent mechanisms and is effective even in cells from SMA patients non-responsive to valproate. Hum Mol Genet 18: 3645-3658 [Abstract] [Full Text]
Boon, K.-L., Xiao, S., McWhorter, M. L., Donn, T., Wolf-Saxon, E., Bohnsack, M. T., Moens, C. B., Beattie, C. E. (2009). Zebrafish survival motor neuron mutants exhibit presynaptic neuromuscular junction defects. Hum Mol Genet 18: 3615-3625 [Abstract] [Full Text]
Workman, E., Saieva, L., Carrel, T. L., Crawford, T. O., Liu, D., Lutz, C., Beattie, C. E., Pellizzoni, L., Burghes, A. H.M. (2009). A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice. Hum Mol Genet 18: 2215-2229 [Abstract] [Full Text]
Briese, M., Esmaeili, B., Fraboulet, S., Burt, E. C., Christodoulou, S., Towers, P. R., Davies, K. E., Sattelle, D. B. (2009). Deletion of smn-1, the Caenorhabditis elegans ortholog of the spinal muscular atrophy gene, results in locomotor dysfunction and reduced lifespan. Hum Mol Genet 18: 97-104 [Abstract] [Full Text]
Shpargel, K. B., Praveen, K., Rajendra, T. K., Matera, A. G. (2009). Gemin3 Is an Essential Gene Required for Larval Motor Function and Pupation in Drosophila. Mol. Biol. Cell 20: 90-101 [Abstract] [Full Text]
Walker, M. P., Rajendra, T.K., Saieva, L., Fuentes, J. L., Pellizzoni, L., Matera, A. G. (2008). SMN complex localizes to the sarcomeric Z-disc and is a proteolytic target of calpain. Hum Mol Genet 17: 3399-3410 [Abstract] [Full Text]
McGovern, V. L., Gavrilina, T. O., Beattie, C. E., Burghes, A. H.M. (2008). Embryonic motor axon development in the severe SMA mouse. Hum Mol Genet 17: 2900-2909 [Abstract] [Full Text]
Kariya, S., Park, G.-H., Maeno-Hikichi, Y., Leykekhman, O., Lutz, C., Arkovitz, M. S., Landmesser, L. T., Monani, U. R. (2008). Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum Mol Genet 17: 2552-2569 [Abstract] [Full Text]
Eisen, J. S., Smith, J. C. (2008). Controlling morpholino experiments: don't stop making antisense. Development 135: 1735-1743 [Abstract] [Full Text]
Oprea, G. E., Krober, S., McWhorter, M. L., Rossoll, W., Muller, S., Krawczak, M., Bassell, G. J., Beattie, C. E., Wirth, B. (2008). Plastin 3 Is a Protective Modifier of Autosomal Recessive Spinal Muscular Atrophy. Science 320: 524-527 [Abstract] [Full Text]
Gavrilina, T. O., McGovern, V. L., Workman, E., Crawford, T. O., Gogliotti, R. G., DiDonato, C. J., Monani, U. R., Morris, G. E., Burghes, A. H.M. (2008). Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle-specific SMN expression has no phenotypic effect. Hum Mol Genet 17: 1063-1075 [Abstract] [Full Text]
Murray, L. M., Comley, L. H., Thomson, D., Parkinson, N., Talbot, K., Gillingwater, T. H. (2008). Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy. Hum Mol Genet 17: 949-962 [Abstract] [Full Text]
Piazzon, N., Rage, F., Schlotter, F., Moine, H., Branlant, C., Massenet, S. (2008). In Vitro and in Cellulo Evidences for Association of the Survival of Motor Neuron Complex with the Fragile X Mental Retardation Protein. J. Biol. Chem. 283: 5598-5610 [Abstract] [Full Text]
Biondi, O., Grondard, C., Lecolle, S., Deforges, S., Pariset, C., Lopes, P., Cifuentes-Diaz, C., Li, H., della Gaspera, B., Chanoine, C., Charbonnier, F. (2008). Exercise-Induced Activation of NMDA Receptor Promotes Motor Unit Development and Survival in a Type 2 Spinal Muscular Atrophy Model Mouse. J. Neurosci. 28: 953-962 [Abstract] [Full Text]
Sumner, C. J. (2007). Molecular Mechanisms of Spinal Muscular Atrophy. J Child Neurol 22: 979-989 [Abstract]
Beattie, C. E., Carrel, T. L., McWhorter, M. L. (2007). Fishing for a Mechanism: Using Zebrafish to Understand Spinal Muscular Atrophy. J Child Neurol 22: 995-1003 [Abstract]
Schmid, A., DiDonato, C. J. (2007). Animal Models of Spinal Muscular Atrophy. J Child Neurol 22: 1004-1012 [Abstract]
van Bergeijk, J., Rydel-Konecke, K., Grothe, C., Claus, P. (2007). The spinal muscular atrophy gene product regulates neurite outgrowth: importance of the C terminus. FASEB J. 21: 1492-1502 [Abstract] [Full Text]
Rajendra, T.K., Gonsalvez, G. B., Walker, M. P., Shpargel, K. B., Salz, H. K., Matera, A. G. (2007). A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle. JCB 176: 831-841 [Abstract] [Full Text]
Ting, C.-H., Lin, C.-W., Wen, S.-L., Hsieh-Li, H.-M., Li, H. (2007). Stat5 constitutive activation rescues defects in spinal muscular atrophy. Hum Mol Genet 16: 499-514 [Abstract] [Full Text]
Setola, V., Terao, M., Locatelli, D., Bassanini, S., Garattini, E., Battaglia, G. (2007). Axonal-SMN (a-SMN), a protein isoform of the survival motor neuron gene, is specifically involved in axonogenesis. Proc. Natl. Acad. Sci. USA 104: 1959-1964 [Abstract] [Full Text]
Carrel, T. L., McWhorter, M. L., Workman, E., Zhang, H., Wolstencroft, E. C., Lorson, C., Bassell, G. J., Burghes, A. H. M., Beattie, C. E. (2006). Survival Motor Neuron Function in Motor Axons Is Independent of Functions Required for Small Nuclear Ribonucleoprotein Biogenesis. J. Neurosci. 26: 11014-11022 [Abstract] [Full Text]
Zhang, H., Xing, L., Rossoll, W., Wichterle, H., Singer, R. H., Bassell, G. J. (2006). Multiprotein Complexes of the Survival of Motor Neuron Protein SMN with Gemins Traffic to Neuronal Processes and Growth Cones of Motor Neurons.. J. Neurosci. 26: 8622-8632 [Abstract] [Full Text]
Sumner, C. J., Kolb, S. J., Harmison, G. G., Jeffries, N. O., Schadt, K., Finkel, R. S., Dreyfuss, G., Fischbeck, K. H. (2006). SMN mRNA and protein levels in peripheral blood: Biomarkers for SMA clinical trials. Neurology 66: 1067-1073 [Abstract] [Full Text]
Jablonka, S., Karle, K., Sandner, B., Andreassi, C., von Au, K., Sendtner, M. (2006). Distinct and overlapping alterations in motor and sensory neurons in a mouse model of spinal muscular atrophy. Hum Mol Genet 15: 511-518 [Abstract] [Full Text]
Olaso, R., Joshi, V., Fernandez, J., Roblot, N., Courageot, S., Bonnefont, J. P., Melki, J. (2006). Activation of RNA metabolism-related genes in mouse but not human tissues deficient in SMN. Physiol. Genomics 24: 97-104 [Abstract] [Full Text]
Gabanella, F., Carissimi, C., Usiello, A., Pellizzoni, L. (2005). The activity of the spinal muscular atrophy protein is regulated during development and cellular differentiation. Hum Mol Genet 14: 3629-3642 [Abstract] [Full Text]
Winkler, C., Eggert, C., Gradl, D., Meister, G., Giegerich, M., Wedlich, D., Laggerbauer, B., Fischer, U. (2005). Reduced U snRNP assembly causes motor axon degeneration in an animal model for spinal muscular atrophy. Genes Dev. 19: 2320-2330 [Abstract] [Full Text]
Jarecki, J., Chen, X., Bernardino, A., Coovert, D. D., Whitney, M., Burghes, A., Stack, J., Pollok, B. A. (2005). Diverse small-molecule modulators of SMN expression found by high-throughput compound screening: early leads towards a therapeutic for spinal muscular atrophy. Hum Mol Genet 14: 2003-2018 [Abstract] [Full Text]
Kernochan, L. E., Russo, M. L., Woodling, N. S., Huynh, T. N., Avila, A. M., Fischbeck, K. H., Sumner, C. J. (2005). The role of histone acetylation in SMN gene expression. Hum Mol Genet 14: 1171-1182 [Abstract] [Full Text]
Gangwani, L., Flavell, R. A., Davis, R. J. (2005). ZPR1 Is Essential for Survival and Is Required for Localization of the Survival Motor Neurons (SMN) Protein to Cajal Bodies. Mol. Cell. Biol. 25: 2744-2756 [Abstract] [Full Text]
Le, T. T., Pham, L. T., Butchbach, M. E.R., Zhang, H. L., Monani, U. R., Coovert, D. D., Gavrilina, T. O., Xing, L., Bassell, G. J., Burghes, A. H.M. (2005). SMN{Delta}7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum Mol Genet 14: 845-857 [Abstract] [Full Text]
Grohmann, K., Rossoll, W., Kobsar, I., Holtmann, B., Jablonka, S., Wessig, C., Stoltenburg-Didinger, G., Fischer, U., Hubner, C., Martini, R., Sendtner, M. (2004). Characterization of Ighmbp2 in motor neurons and implications for the pathomechanism in a mouse model of human spinal muscular atrophy with respiratory distress type 1 (SMARD1). Hum Mol Genet 13: 2031-2042 [Abstract] [Full Text]
Rossoll, W., Jablonka, S., Andreassi, C., Kroning, A.-K., Karle, K., Monani, U. R., Sendtner, M. (2003). Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of {beta}-actin mRNA in growth cones of motoneurons. JCB 163: 801-812 [Abstract] [Full Text]