RGD Reference Report - Slit2/Robo1 promotes synaptogenesis and functional recovery of spinal cord injury. - Rat Genome Database

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Slit2/Robo1 promotes synaptogenesis and functional recovery of spinal cord injury.

Authors: Li, Yang  Gao, Yan  Xu, Xueqin  Shi, Ruoshi  Liu, Juying  Yao, Wanjun  Ke, Changbin 
Citation: Li Y, etal., Neuroreport. 2017 Jan 18;28(2):75-81. doi: 10.1097/WNR.0000000000000715.
RGD ID: 243048440
Pubmed: PMID:27893610   (View Abstract at PubMed)
DOI: DOI:10.1097/WNR.0000000000000715   (Journal Full-text)

Neuronal network reconstruction is a pivotal determinant for functional recovery after spinal cord injury (SCI), the process of which includes synaptogenesis. Slit2 protein has been identified as a key regulator of axon regeneration and synapse formation in the vertebrate. Meanwhile, RhoA is the converging cascade of inhibitory molecules that interrupt synaptic plasticity in SCI. In the present study, we investigated the interaction among Slit2, Robo1, and RhoA and the potential roles of Slit2 in the pathological process of SCI. We showed that Slit2 was decreased, whereas Robo1 and RhoA were increased in the same surviving neurons in the spinal cord following SCI. We also found that inhibition of Slit2 led to upregulation of the expression of Robo1 and RhoA. However, the severe dysfunctions of the locomotor performance induced by SCI were reversed by treatments of Slit2-N, the active portion of Slit2, knockdown of Robo1 by the RNAi lentivirus, or inhibition of RhoA by the C3 exoenzyme, respectively. Further results suggested that downregulation of Slit2 and therefore upregulation of Robo1 and RhoA inhibited the activity of growth cone and hindered the formation of new synapses of surviving neurons near the injury sites of the spinal cord following SCI. Our study indicated a new mechanism of deficiency of synaptogenesis during the development of SCI and provided a potential strategy for the treatment of SCI.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Spinal Cord Injuries  ISORhoa (Rattus norvegicus)243048440; 243048440mRNA and protein:increased expression:spinal cord:RGD 
Spinal Cord Injuries  ISORobo1 (Rattus norvegicus)243048440; 243048440mRNA and protein:increased expression:spinal cord:RGD 
Spinal Cord Injuries  IEP 243048440; 243048440mRNA and protein:increased expression:spinal cord:RGD 
Spinal Cord Injuries  ISOSlit2 (Rattus norvegicus)243048440; 243048440mRNA and protein:decreased expression:spinal cord:RGD 
Spinal Cord Injuries  IEP 243048440mRNA and protein:decreased expression:spinal cord:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of synapse assembly  IMP 243048440; 243048440 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rhoa  (ras homolog family member A)
Robo1  (roundabout guidance receptor 1)
Slit2  (slit guidance ligand 2)

Genes (Mus musculus)
Rhoa  (ras homolog family member A)
Robo1  (roundabout guidance receptor 1)
Slit2  (slit guidance ligand 2)

Genes (Homo sapiens)
RHOA  (ras homolog family member A)
ROBO1  (roundabout guidance receptor 1)
SLIT2  (slit guidance ligand 2)


Additional Information