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Novel Insights into NeuN: from Neuronal Marker to Splicing Regulator

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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.

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Acknowledgments

We would like to thank Dr. Kimberly Yasutis for proofreading and offering corrections and suggestions regarding the manuscript. This work was supported by grants from the National Natural Science Foundation of China (No. 81100891, No. 81471226) and the Natural Science Foundation Project of CQ (No. CSTC 2012 jjB10019).

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Authors and Affiliations

  1. Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People’s Republic of China

    Wei Duan

  2. Department of Pediatrics, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People’s Republic of China

    Yu-Ping Zhang

  3. Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People’s Republic of China

    Zhi Hou & Chun-Qing Zhang

  4. Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, 37232, USA

    Chen Huang & He Zhu

  5. Department of Biological Sciences, Vanderbilt University, Nashville, TN, 37232, USA

    He Zhu

  6. Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA

    He Zhu

  7. The Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, 37232, USA

    He Zhu

  8. Department of Rehabilitation and Physical Therapy, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People’s Republic of China

    Qing Yin

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  1. Wei Duan
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  2. Yu-Ping Zhang
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  3. Zhi Hou
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  4. Chen Huang
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  5. He Zhu
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  6. Chun-Qing Zhang
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  7. Qing Yin
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Corresponding authors

Correspondence to Chun-Qing Zhang or Qing Yin.

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Duan, W., Zhang, YP., Hou, Z. et al. Novel Insights into NeuN: from Neuronal Marker to Splicing Regulator. Mol Neurobiol 53, 1637–1647 (2016). https://doi.org/10.1007/s12035-015-9122-5

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  • DOI: https://doi.org/10.1007/s12035-015-9122-5

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