Genetic and chemical modulation of spastin-dependent axon outgrowth in zebrafish embryos indicates a role for impaired microtubule dynamics in hereditary spastic paraplegia.

ABSTRACT: Mutations in the SPAST (SPG4) gene, which encodes the microtubule-severing protein spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP). Following on from previous work in our laboratory showing that spastin is required for axon outgrowth, we report here that the related microtubule-severing protein katanin is also required for axon outgrowth in vivo. Using confocal time-lapse imaging, we have identified requirements for spastin and katanin in maintaining normal axonal microtubule dynamics and growth cone motility in vivo, supporting a model in which microtubule severing is required for concerted growth of neuronal microtubules. Simultaneous knockdown of spastin and katanin caused a more severe phenotype than did individual knockdown of either gene,

SUBMITTER: Butler R 

PROVIDER: S-EPMC2965401 | biostudies-literature | 2010 Nov-Dec

REPOSITORIES: biostudies-literature