Spatacsin and spastizin act in the same pathway required for proper spinal motor neuron axon outgrowth in zebrafish.
Neurobiology of Disease. 2012-12-01; 48(3): 299-308
DOI: 10.1016/j.nbd.2012.07.003
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1. Neurobiol Dis. 2012 Dec;48(3):299-308. doi: 10.1016/j.nbd.2012.07.003. Epub 2012
Jul 16.
Spatacsin and spastizin act in the same pathway required for proper spinal motor
neuron axon outgrowth in zebrafish.
Martin E(1), Yanicostas C, Rastetter A, Alavi Naini SM, Maouedj A, Kabashi E,
Rivaud-Péchoux S, Brice A, Stevanin G, Soussi-Yanicostas N.
Author information:
(1)INSERM, U975, 75013 Paris, France.
Hereditary spastic paraplegias (HSPs) are rare neurological conditions caused by
degeneration of the long axons of the cerebrospinal tracts, leading to locomotor
impairment and additional neurological symptoms. There are more than 40 different
causative genes, 24 of which have been identified, including SPG11 and SPG15
mutated in complex clinical forms. Since the vast majority of the causative
mutations lead to loss of function of the corresponding proteins, we made use of
morpholino-oligonucleotide (MO)-mediated gene knock-down to generate zebrafish
models of both SPG11 and SPG15 and determine how invalidation of the causative
genes (zspg11 and zspg15) during development might contribute to the disease.
Micro-injection of MOs targeting each gene caused locomotor impairment and
abnormal branching of spinal cord motor neurons at the neuromuscular junction.
More severe phenotypes with abnormal tail developments were also seen. Moreover,
partial depletion of both proteins at sub-phenotypic levels resulted in the same
phenotypes, suggesting for the first time, in vivo, a genetic interaction between
these genes. In conclusion, the zebrafish orthologues of the SPG11 and SPG15
genes are important for proper development of the axons of spinal motor neurons
and likely act in a common pathway to promote their proper path finding towards
the neuromuscular junction.
Copyright © 2012 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nbd.2012.07.003
PMID: 22801083 [Indexed for MEDLINE]