The transcription factor Sox11 promotes nerve regeneration through activation of the regeneration-associated gene Sprr1a.
Factors that enhance the intrinsic growth potential of adult neurons are key players in the successful repair and regeneration of neurons following injury. Injury-induced activation of transcription factors has a central role in this process because they regulate expression of regeneration-associated genes. Sox11 is a developmentally expressed transcription factor that is significantly induced in adult neurons in response to injury. Its function in injured neurons is however undefined. Here, we report studies that use herpes simplex virus (HSV)-vector-mediated expression of Sox11 in adult sensory neurons to assess the effect of Sox11 overexpression on neuron regeneration. Cultured mouse dorsal root ganglia (DRG) neurons transfected with HSV-Sox11 exhibited increased neurite elongation and branching relative to naïve and HSV-vector control treated neurons. Neurons from mice injected in foot skin with HSV-Sox11 exhibited accelerated regeneration of crushed saphenous nerves as indicated by faster regrowth of axons and nerve fibers to the skin, increased myelin thickness and faster return of nerve and skin sensitivity. Downstream targets of HSV-Sox11 were examined by analyzing changes in gene expression of known regeneration-associated genes. This analysis in combination with mutational and chromatin immunoprecipitation assays indicates that the ability of Sox11 to accelerate in vivo nerve regeneration is dependent on its transcriptional activation of the regeneration-associated gene, small proline rich protein 1a (Sprr1a). This finding reveals a new functional linkage between Sox11 and Sprr1a in adult peripheral neuron regeneration.
Department of Medicine, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Xiaotang
X
Jing
Ting
T
Wang
Shaohua
S
Huang
Joseph C
JC
Glorioso
Kathryn M
KM
Albers
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D005822:Genetic Vectors / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis / Q000235:genetics; D009409:Nerve Crush / Q000379:methods; D009412:Nerve Fibers / Q000473:pathology; D009416:Nerve Regeneration / Q000235:genetics* / Q000502:physiology; D016501:Neurites / Q000502:physiology; D010147:Pain Measurement; D059348:Peripheral Nerve Injuries / Q000473:pathology* / Q000503:physiopathology; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000473:pathology / Q000502:physiology; D018139:Simplexvirus / Q000235:genetics; D012867:Skin / Q000294:innervation; D013997:Time Factors; D014162:Transfection / Q000379:methods
D055233:Cornified Envelope Proline-Rich Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D055751:SOXC Transcription Factors; C490793:Sox11 protein, mouse; C524532:Sprr1a protein, mouse; D049452:Green Fluorescent Proteins