LSD1 co-repressor Rcor2 orchestrates neurogenesis in the developing mouse brain

Yixuan Wang, Qian Wu, Peng Yang, Chenfei Wang, Jing Liu, Wenyu Ding, Wensu Liu, Ye Bai, Yuanyuan Yang, Hong Wang, Shaorong Gao () and Xiaoqun Wang ()
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Yixuan Wang: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, School of Life Sciences and Technology, Tongji University
Qian Wu: State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Beijing MRI Centre for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing Institute for Brain Disorders, 8803, 8th Building, 15 Datun Road, Chaoyang District,
Peng Yang: National Institute of Biological Sciences (NIBS)
Chenfei Wang: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, School of Life Sciences and Technology, Tongji University
Jing Liu: State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Beijing MRI Centre for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing Institute for Brain Disorders, 8803, 8th Building, 15 Datun Road, Chaoyang District,
Wenyu Ding: State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Beijing MRI Centre for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing Institute for Brain Disorders, 8803, 8th Building, 15 Datun Road, Chaoyang District,
Wensu Liu: State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Beijing MRI Centre for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing Institute for Brain Disorders, 8803, 8th Building, 15 Datun Road, Chaoyang District,
Ye Bai: State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Beijing MRI Centre for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing Institute for Brain Disorders, 8803, 8th Building, 15 Datun Road, Chaoyang District,
Yuanyuan Yang: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, School of Life Sciences and Technology, Tongji University
Hong Wang: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, School of Life Sciences and Technology, Tongji University
Shaorong Gao: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, School of Life Sciences and Technology, Tongji University
Xiaoqun Wang: State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Beijing MRI Centre for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing Institute for Brain Disorders, 8803, 8th Building, 15 Datun Road, Chaoyang District,

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Epigenetic regulatory complexes play key roles in the modulation of transcriptional regulation underlying neural stem cell (NSC) proliferation and progeny specification. How specific cofactors guide histone demethylase LSD1/KDM1A complex to regulate distinct NSC-related gene activation and repression in cortical neurogenesis remains unclear. Here we demonstrate that Rcor2, a co-repressor of LSD1, is mainly expressed in the central nervous system (CNS) and plays a key role in epigenetic regulation of cortical development. Depletion of Rcor2 results in reduced NPC proliferation, neuron population, neocortex thickness and brain size. We find that Rcor2 directly targets Dlx2 and Shh, and represses their expressions in developing neocortex. In addition, inhibition of Shh signals rescues the neurogenesis defects caused by Rcor2 depletion both in vivo and in vitro. Hence, our findings suggest that co-repressor Rcor2 is critical for cortical development by repressing Shh signalling pathway in dorsal telencephalon.

Date: 2016
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DOI: 10.1038/ncomms10481

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