Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy

Research output: Contribution to journalResearch articleContributedpeer-review


  • James N. Sleigh - , University of Oxford (Author)
  • Antón Barreiro-Iglesias - , University of Edinburgh (Author)
  • Peter L. Oliver - , University of Oxford (Author)
  • Angeliki Biba - , University of Oxford (Author)
  • Thomas Becker - , University of Edinburgh (Author)
  • Kay E. Davies - , University of Oxford (Author)
  • Catherina G. Becker - , University of Edinburgh (Author)
  • Kevin Talbot - , University of Oxford (Author)


Spinal muscular atrophy (SMA) is characterized by the selective loss of spinal motor neurons owing to reduced levels of survival motor neuron (Smn) protein. In addition to its well-established role in assembling constituents of the spliceosome, diverse cellular functions have been proposed for Smn, but the reason whylow levels of this widely expressed protein result in selective motor neuron pathology is still debated. In longitudinal studies of exon-level changes in SMA mouse model tissues, designed to determine the contribution of splicing dysfunction to the disease, we have previously shown that a generalized defect in splicing is unlikely to play a causative role in SMA. Nevertheless, we identified a small subset of genes that were alternatively spliced in the spinal cord compared with control mice before symptom onset, indicating a possible mechanistic role in disease. Here, we haveperformed functional studies ofoneof these genes,chondrolectin (Chodl),knowntobehighly expressed in motor neurons and important for correct motor axon outgrowth in zebrafish. Using in vitro and in vivo models of SMA, we demonstrate altered expression of Chodl in SMA mouse spinal motor neurons, show that Chodl has distinct effects on cell survival and neurite outgrowth and that increasing the expression of chodl can rescue motor neuron outgrowth defects in Smn-depleted zebrafish. Our findings thus link the dysregulation of Chodl to the pathophysiology of motor neuron degeneration in SMA.


Original languageEnglish
Pages (from-to)855-869
Number of pages15
JournalHuman molecular genetics
Issue number4
Publication statusPublished - Feb 2014
Externally publishedYes

External IDs

PubMed 24067532