BMP-and neuropilin 1-mediated motor axon navigation relies on spastin alternative translation

Nicolas Jardin, François Giudicelli, Daniel Ten Martıń, Anaïs Vitrac, Steṕhanie De Gois, Rachel Allison, Corinne Houart, Evan Reid, Jamilé Hazan, Coralie Fassier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
243 Downloads (Pure)


Functional analyses of genes responsible for neurodegenerative disorders have unveiled crucial links between neurodegenerative processes and key developmental signalling pathways. Mutations in SPG4-encoding spastin cause hereditary spastic paraplegia (HSP). Spastin is involved in diverse cellular processes that couple microtubule severing to membrane remodelling. Two main spastin isoforms are synthesised from alternative translational start sites (M1 and M87). However, their specific roles in neuronal development and homeostasis remain largely unknown. To selectively unravel their neuronal function, we blocked spastin synthesis from each initiation codon during zebrafish development and performed rescue analyses. The knockdown of each isoform led to different motor neuron and locomotion defects, which were not rescued by the selective expression of the other isoform. Notably, both morphant neuronal phenotypes were observed in a CRISPR/Cas9 spastin mutant. We next showed that M1 spastin, together with HSP proteins atlastin 1 and NIPA1, drives motor axon targeting by repressing BMP signalling, whereas M87 spastin acts downstream of neuropilin 1 to control motor neuron migration. Our data therefore suggest that defective BMP and neuropilin 1 signalling may contribute to the motor phenotype in a vertebrate model of spastin depletion.

Original languageEnglish
Article numberdev162701
JournalDevelopment (Cambridge)
Issue number17
Publication statusPublished - 1 Sept 2018


  • Axon navigation
  • BMP signalling
  • Hereditary spastic paraplegia
  • Neuropilin 1
  • Spastin
  • Zebrafish


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