Slit2/Robo1 is a conserved ligand-receptor system,which greatly affects the distribution,migration,axon guidance and branching of neuron cells.Slit2 and its transmembrane receptor Robo1 have different distribution pat...Slit2/Robo1 is a conserved ligand-receptor system,which greatly affects the distribution,migration,axon guidance and branching of neuron cells.Slit2 and its transmembrane receptor Robo1 have different distribution patterns in gliomas.The expression of Slit2 is at very low levels in pilocytic astrocytoma,fibrillary astrocytoma and glioblastoma,while Robo1 is highly expressed in different grades of gliomas at both mRNA and protein levels.Acquisition of insidious invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways.Although the specific mechanisms of tumor-suppressive effect of Slit2/Robo1 have not been elucidated,it has been proved that Slit2/Robo1 signaling inhibits glioma cellmigration and invasion by inactivation of Cdc42-GTP.With the research development on the molecular mechanisms of Slit2/Robo1 signaling in glioma invasion and migration,Slit2/Robo1 signaling may become a potential target for glioma prevention and treatment.展开更多
The Slit family of axon guidance cues act as repulsive molecules for precise axon pathfinding and neuronal migration during nervous system development through interactions with specific Robo receptors.Although we prev...The Slit family of axon guidance cues act as repulsive molecules for precise axon pathfinding and neuronal migration during nervous system development through interactions with specific Robo receptors.Although we previously reported that Slit1–3 and their receptors Robo1 and Robo2 are highly expressed in the adult mouse peripheral nervous system,how this expression changes after injury has not been well studied.Herein,we constructed a peripheral nerve injury mouse model by transecting the right sciatic nerve.At 14 days after injury,quantitative real-time polymerase chain reaction was used to detect mRNA expression of Slit1–3 and Robo1–2 in L4–5 spinal cord and dorsal root ganglia,as well as the sciatic nerve.Immunohistochemical analysis was performed to examine Slit1–3,Robo1–2,neurofilament heavy chain,F4/80,and vimentin in L4–5 spinal cord,L4 dorsal root ganglia,and the sciatic nerve.Co-expression of Slit1–3 and Robo1–2 in L4 dorsal root ganglia was detected by in situ hybridization.In addition,Slit1–3 and Robo1–2 protein expression in L4–5 spinal cord,L4 dorsal root ganglia,and sciatic nerve were detected by western blot assay.The results showed no significant changes of Slit1–3 or Robo1–2 mRNA expression in the spinal cord within 14 days after injury.In the dorsal root ganglion,Slit1–3 and Robo1–2 mRNA expression were initially downregulated within 4 days after injury;however,Robo1–2 mRNA expression returned to the control level,while Slit1–3 mRNA expression remained upregulated during regeneration from 4–14 days after injury.In the sciatic nerve,Slit1–3 and their receptors Robo1–2 were all expressed in the proximal nerve stump;however,Slit1,Slit2,and Robo2 were barely detectable in the nerve bridge and distal nerve stump within 14 days after injury.Slit3 was highly ex-pressed in macrophages surrounding the nerve bridge and slightly downregulated in the distal nerve stump within 14 days after injury.Robo1 was upregulated in vimentin-positive cells and migrating Schwann cells inside the nerve bridge.Robo1 was also upregulated in Schwann cells of the distal nerve stump within 14 days after injury.Our findings indicate that Slit3 is the major ligand expressed in the nerve bridge and distal nerve stump during peripheral nerve regeneration,and Slit3/Robo signaling could play a key role in peripheral nerve repair after injury.This study was approved by Plymouth University Animal Welfare Ethical Review Board (approval No.30/3203) on April 12,2014.展开更多
基金supported by the grants of National Natural Science Foundation of China(No.30700253,30800355)the Program for Changjiang Scholars and Innovative Research Team in University,Ministry of Education,China(No.IRT0734)
文摘Slit2/Robo1 is a conserved ligand-receptor system,which greatly affects the distribution,migration,axon guidance and branching of neuron cells.Slit2 and its transmembrane receptor Robo1 have different distribution patterns in gliomas.The expression of Slit2 is at very low levels in pilocytic astrocytoma,fibrillary astrocytoma and glioblastoma,while Robo1 is highly expressed in different grades of gliomas at both mRNA and protein levels.Acquisition of insidious invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways.Although the specific mechanisms of tumor-suppressive effect of Slit2/Robo1 have not been elucidated,it has been proved that Slit2/Robo1 signaling inhibits glioma cellmigration and invasion by inactivation of Cdc42-GTP.With the research development on the molecular mechanisms of Slit2/Robo1 signaling in glioma invasion and migration,Slit2/Robo1 signaling may become a potential target for glioma prevention and treatment.
基金supported by the National Natural Science Foundation of China,No.81371353(to XPD)
文摘The Slit family of axon guidance cues act as repulsive molecules for precise axon pathfinding and neuronal migration during nervous system development through interactions with specific Robo receptors.Although we previously reported that Slit1–3 and their receptors Robo1 and Robo2 are highly expressed in the adult mouse peripheral nervous system,how this expression changes after injury has not been well studied.Herein,we constructed a peripheral nerve injury mouse model by transecting the right sciatic nerve.At 14 days after injury,quantitative real-time polymerase chain reaction was used to detect mRNA expression of Slit1–3 and Robo1–2 in L4–5 spinal cord and dorsal root ganglia,as well as the sciatic nerve.Immunohistochemical analysis was performed to examine Slit1–3,Robo1–2,neurofilament heavy chain,F4/80,and vimentin in L4–5 spinal cord,L4 dorsal root ganglia,and the sciatic nerve.Co-expression of Slit1–3 and Robo1–2 in L4 dorsal root ganglia was detected by in situ hybridization.In addition,Slit1–3 and Robo1–2 protein expression in L4–5 spinal cord,L4 dorsal root ganglia,and sciatic nerve were detected by western blot assay.The results showed no significant changes of Slit1–3 or Robo1–2 mRNA expression in the spinal cord within 14 days after injury.In the dorsal root ganglion,Slit1–3 and Robo1–2 mRNA expression were initially downregulated within 4 days after injury;however,Robo1–2 mRNA expression returned to the control level,while Slit1–3 mRNA expression remained upregulated during regeneration from 4–14 days after injury.In the sciatic nerve,Slit1–3 and their receptors Robo1–2 were all expressed in the proximal nerve stump;however,Slit1,Slit2,and Robo2 were barely detectable in the nerve bridge and distal nerve stump within 14 days after injury.Slit3 was highly ex-pressed in macrophages surrounding the nerve bridge and slightly downregulated in the distal nerve stump within 14 days after injury.Robo1 was upregulated in vimentin-positive cells and migrating Schwann cells inside the nerve bridge.Robo1 was also upregulated in Schwann cells of the distal nerve stump within 14 days after injury.Our findings indicate that Slit3 is the major ligand expressed in the nerve bridge and distal nerve stump during peripheral nerve regeneration,and Slit3/Robo signaling could play a key role in peripheral nerve repair after injury.This study was approved by Plymouth University Animal Welfare Ethical Review Board (approval No.30/3203) on April 12,2014.
