Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy.
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,...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2014
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| _version_ | 1797079377655103488 |
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| author | Sleigh, J Barreiro-Iglesias, A Oliver, P Biba, A Becker, T Davies, K Becker, C Talbot, K |
| author_facet | Sleigh, J Barreiro-Iglesias, A Oliver, P Biba, A Becker, T Davies, K Becker, C Talbot, K |
| author_sort | Sleigh, J |
| collection | OXFORD |
| description | 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 why low 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 have performed functional studies of one of these genes, chondrolectin (Chodl), known to be highly 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. |
| first_indexed | 2024-03-07T00:45:01Z |
| format | Journal article |
| id | oxford-uuid:845479b6-8bc0-4b98-b65b-26067e35fd20 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:45:01Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:845479b6-8bc0-4b98-b65b-26067e35fd202022-03-26T21:50:25ZChondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:845479b6-8bc0-4b98-b65b-26067e35fd20EnglishSymplectic Elements at Oxford2014Sleigh, JBarreiro-Iglesias, AOliver, PBiba, ABecker, TDavies, KBecker, CTalbot, KSpinal 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 why low 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 have performed functional studies of one of these genes, chondrolectin (Chodl), known to be highly 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. |
| spellingShingle | Sleigh, J Barreiro-Iglesias, A Oliver, P Biba, A Becker, T Davies, K Becker, C Talbot, K Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy. |
| title | Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy. |
| title_full | Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy. |
| title_fullStr | Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy. |
| title_full_unstemmed | Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy. |
| title_short | Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy. |
| title_sort | chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy |
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