title: Novel Insights into NeuN: from Neuronal Marker to Splicing Regulator.
abstract: Neuronal nuclei (NeuN) is a well-recognized "marker" that is detected exclusively in post-mitotic neurons and was initially identified through an immunological screen to produce neuron-specific antibodies. Immunostaining evidence indicates that NeuN is distributed in the nuclei of mature neurons in nearly all parts of the vertebrate nervous system. NeuN is highly conserved among species and is stably expressed during specific stages of development. Therefore, NeuN has been considered to be a reliable marker of mature neurons for the past two decades. However, this role has been challenged by recent studies indicating that NeuN staining is variable and even absent during certain diseases and specific physiological states. More importantly, despite the widespread use of the anti-NeuN antibody, the natural identity of the NeuN protein remained elusive for 17 years. NeuN was recently eventually identified as an epitope of Rbfox3, which is a novel member of the Rbfox1 family of splicing factors. This identification might provide a novel perspective on NeuN expression during both physiological and pathological conditions. This review summarizes the current progress on the biochemical identity and biological significance of NeuN and recommends caution when applying NeuN immunoreactivity as a definitive marker of mature neurons in certain diseases and specific physiological states.
authors: Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.
authors: Wei
authors: W
authors: Duan
authors: Department of Pediatrics, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.
authors: Yu-Ping
authors: YP
authors: Zhang
authors: Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.
authors: Zhi
authors: Z
authors: Hou
authors: Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, 37232, USA.
authors: Chen
authors: C
authors: Huang
authors: Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, 37232, USA.|Department of Biological Sciences, Vanderbilt University, Nashville, TN, 37232, USA.|Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA.|The Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, 37232, USA.
authors: He
authors: H
authors: Zhu
authors: Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China. cqzhang@tmmu.edu.cn.
authors: Chun-Qing
authors: CQ
authors: Zhang
authors: Department of Rehabilitation and Physical Therapy, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China. qingyin646891@yahoo.com.
authors: Qing
authors: Q
authors: Yin
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D034961:Antigens, Nuclear / Q000502:physiology*; D019771:Axotomy; D015415:Biomarkers; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D000939:Epitopes; D005786:Gene Expression Regulation; D006801:Humans; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism; D065886:Neurodevelopmental Disorders / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000737:chemistry; D000072260:RNA Splicing Factors / Q000502:physiology*; D013312:Stress, Physiological; D014714:Vertebrates / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D015415:Biomarkers; D000939:Epitopes; D009419:Nerve Tissue Proteins; D000072260:RNA Splicing Factors; C506808:neuronal nuclear antigen NeuN, human
keywords: Mature neurons; NeuN; Neuronal marker; Rbfox3; Splicing regulator