The peripheral nervous system has an astonishing ability to regenerate following a compression or crush injury;however,the potential for full repair following a transection injury is much less.Currently,the major clin...The peripheral nervous system has an astonishing ability to regenerate following a compression or crush injury;however,the potential for full repair following a transection injury is much less.Currently,the major clinical challenge for peripheral nerve repair come from long gaps between the proximal and distal nerve stumps,which prevent regenerating axons reaching the distal nerve.Precise axon targeting during nervous system development is controlled by families of axon guidance molecules including Netrins,Slits,Ephrins and Semaphorins.Several recent studies have indicated key roles of Netrin1,Slit3 and EphrinB2 signalling in controlling the formation of new nerve bridge tissue and precise axon regeneration after peripheral nerve transection injury.Inside the nerve bridge,nerve fibroblasts express EphrinB2 while migrating Schwann cells express the receptor EphB2.EphrinB2/EphB2 signalling between nerve fibroblasts and migrating Schwann cells is required for Sox2 upregulation in Schwann cells and the formation of Schwann cell cords within the nerve bridge to allow directional axon growth to the distal nerve stump.Macrophages in the outermost layer of the nerve bridge express Slit3 while migrating Schwann cells and regenerating axons express the receptor Robo1;within Schwann cells,Robo1 expression is also Sox2-dependent.Slit3/Robo1 signalling is required to keep migrating Schwann cells and regenerating axons inside the nerve bridge.In addition to the Slit3/Robo1 signalling system,migrating Schwann cells also express Netrin1 and regenerating axons express the DCC receptor.It appears that migrating Schwann cells could also use Netrin1 as a guidance cue to direct regenerating axons across the peripheral nerve gap.Engineered neural tissues have been suggested as promising alternatives for the repair of large peripheral nerve gaps.Therefore,understanding the function of classic axon guidance molecules in nerve bridge formation and their roles in axon regeneration could be highly beneficial in developing engineered neural tissue for more effective peripheral nerve repair.展开更多
Leucine-rich repeats containing 4(LRRC4,also named netrin-G ligand 2[NGL-2])is a member of the NetrinGs ligands(NGLs)family.As a gene with relatively high and specific expression in brain,it is a member of the leucine...Leucine-rich repeats containing 4(LRRC4,also named netrin-G ligand 2[NGL-2])is a member of the NetrinGs ligands(NGLs)family.As a gene with relatively high and specific expression in brain,it is a member of the leucine-rich repeat superfamily and has been proven to be a suppressor gene for gliomas,thus being involved in gliomagenesis.LRRC4 is the core of microRNA-dependent multi-phase regulatory loops that inhibit the proliferation and invasion of glioblastoma(GB)cells,including LRRC4/NGL2-activator protein 2(AP2)-microRNA(miR)182-LRRC4 and LRRC4-miR185-DNA methyltransferase 1(DNMT1)-LRRC4/specific protein 1(SP1)-DNMT1-LRRC4.In this review,we demonstrated LRRC4 as a new member of the partitioning-defective protein(PAR)polarity complex that promotes axon differentiation,mediates the formation and plasticity of synapses,and assists information input to the hippocampus and storage of memory.As an important synapse regulator,aberrant expression of LRRC4 has been detected in autism,spinal injury and GBs.LRRC4 is a candidate susceptibility gene for autism and a neuro-protective factor in spinal nerve damage.In GBs,LRRC4 is a novel inhibitor of autophagy,and an inhibitor of protein–protein interactions involving in temozolomide resistance,tumor immune microenvironment,and formation of circular RNA.展开更多
文摘The peripheral nervous system has an astonishing ability to regenerate following a compression or crush injury;however,the potential for full repair following a transection injury is much less.Currently,the major clinical challenge for peripheral nerve repair come from long gaps between the proximal and distal nerve stumps,which prevent regenerating axons reaching the distal nerve.Precise axon targeting during nervous system development is controlled by families of axon guidance molecules including Netrins,Slits,Ephrins and Semaphorins.Several recent studies have indicated key roles of Netrin1,Slit3 and EphrinB2 signalling in controlling the formation of new nerve bridge tissue and precise axon regeneration after peripheral nerve transection injury.Inside the nerve bridge,nerve fibroblasts express EphrinB2 while migrating Schwann cells express the receptor EphB2.EphrinB2/EphB2 signalling between nerve fibroblasts and migrating Schwann cells is required for Sox2 upregulation in Schwann cells and the formation of Schwann cell cords within the nerve bridge to allow directional axon growth to the distal nerve stump.Macrophages in the outermost layer of the nerve bridge express Slit3 while migrating Schwann cells and regenerating axons express the receptor Robo1;within Schwann cells,Robo1 expression is also Sox2-dependent.Slit3/Robo1 signalling is required to keep migrating Schwann cells and regenerating axons inside the nerve bridge.In addition to the Slit3/Robo1 signalling system,migrating Schwann cells also express Netrin1 and regenerating axons express the DCC receptor.It appears that migrating Schwann cells could also use Netrin1 as a guidance cue to direct regenerating axons across the peripheral nerve gap.Engineered neural tissues have been suggested as promising alternatives for the repair of large peripheral nerve gaps.Therefore,understanding the function of classic axon guidance molecules in nerve bridge formation and their roles in axon regeneration could be highly beneficial in developing engineered neural tissue for more effective peripheral nerve repair.
基金National Natural Science Foundation of China(No.82073096)Hunan Provincial Natural Science Foundation of China(No.2022JJ40578)
文摘Leucine-rich repeats containing 4(LRRC4,also named netrin-G ligand 2[NGL-2])is a member of the NetrinGs ligands(NGLs)family.As a gene with relatively high and specific expression in brain,it is a member of the leucine-rich repeat superfamily and has been proven to be a suppressor gene for gliomas,thus being involved in gliomagenesis.LRRC4 is the core of microRNA-dependent multi-phase regulatory loops that inhibit the proliferation and invasion of glioblastoma(GB)cells,including LRRC4/NGL2-activator protein 2(AP2)-microRNA(miR)182-LRRC4 and LRRC4-miR185-DNA methyltransferase 1(DNMT1)-LRRC4/specific protein 1(SP1)-DNMT1-LRRC4.In this review,we demonstrated LRRC4 as a new member of the partitioning-defective protein(PAR)polarity complex that promotes axon differentiation,mediates the formation and plasticity of synapses,and assists information input to the hippocampus and storage of memory.As an important synapse regulator,aberrant expression of LRRC4 has been detected in autism,spinal injury and GBs.LRRC4 is a candidate susceptibility gene for autism and a neuro-protective factor in spinal nerve damage.In GBs,LRRC4 is a novel inhibitor of autophagy,and an inhibitor of protein–protein interactions involving in temozolomide resistance,tumor immune microenvironment,and formation of circular RNA.
