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Hairy and Enhancer of Split 6 (Hes6) Deficiency in Mouse Impairs Neuroblast Differentiation in Dentate Gyrus Without Affecting Cell Proliferation and Integration into Mature Neurons

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Abstract

Hes6 is a member of the hairy-enhancer of split homolog (Hes) family of transcription factors and interacts with other Hes family genes. During development, Hes genes are expressed in neural stem cells and progenitor cells. However, the role of Hes6 in adult hippocampal neurogenesis remains unclear. We therefore investigated the effects of Hes6 on adult hippocampal neurogenesis, by comparing Hes6 knockout and wild-type mice. To this end, we immunostained for markers of neural stem cells and progenitor cells (nestin), proliferating cells (Ki67), post-mitotic neuroblasts and immature neurons (doublecortin, DCX), mature neuronal cells (NeuN), and astrocyte (S100β). We also injected 5-bromo-2′-deoxyuridine (BrdU) to trace the fate of mitotic cells. Nestin- and Ki67-positive proliferating cells did now show any significant differences between wild and knockout groups. Hes6 knockout negatively affects neuroblast differentiation based on DCX immunohistochemistry. On the contrary, the ratio of the BrdU and NeuN double-positive cells did not show any significance, even though it was slightly higher in the knockout group. These results suggest that Hes6 is involved in the regulation of neuroblast differentiation during adult neurogenesis, but does not influence integration into mature neurons.

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Acknowledgments

This research was supported by the Korea Mouse Phenotyping Project of the Ministry of Science, ICT & Future Planning through the National Research Foundation (2013M3A9D5072550), and the Bio-industry Technology Development Program, Ministry of Agriculture, Food and Rural Affairs (311054-03-2-HD110) to Seong JK.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea

    Sung Min Nam, Yo Na Kim, Jong Whi Kim, Dong Soo Kyeong, Seo Hyun Lee, Yeri Son, Jae Hoon Shin, Yeo Sung Yoon & Je Kyung Seong

  2. BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    Sung Min Nam, Yo Na Kim, Jong Whi Kim, Dong Soo Kyeong, Seo Hyun Lee, Yeri Son, Jae Hoon Shin, Yeo Sung Yoon & Je Kyung Seong

  3. KMPC (Korea Mouse Phenotyping Center), Seoul National University, Seoul, 151-742, South Korea

    Sung Min Nam, Yo Na Kim, Jong Whi Kim, Dong Soo Kyeong, Seo Hyun Lee, Yeri Son, Jae Hoon Shin, Yeo Sung Yoon & Je Kyung Seong

  4. Interdisciplinary Program for Bioinformatics, Program for Cancer Biology and BIO-MAX Institute, Seoul National University, Seoul, 151-742, South Korea

    Je Kyung Seong

  5. Department of Life Sciences and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul, 120-750, South Korea

    Jaesang Kim

  6. Department of Biomedical Laboratory Science, College of Biomedical Sciences, Soonchunhyang University, Asan, 336-745, South Korea

    Sun Shin Yi

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  1. Sung Min Nam
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Correspondence to Yeo Sung Yoon or Je Kyung Seong.

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Nam, S.M., Kim, Y.N., Kim, J.W. et al. Hairy and Enhancer of Split 6 (Hes6) Deficiency in Mouse Impairs Neuroblast Differentiation in Dentate Gyrus Without Affecting Cell Proliferation and Integration into Mature Neurons. Cell Mol Neurobiol 36, 57–67 (2016). https://doi.org/10.1007/s10571-015-0220-8

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