title: LSD1 co-repressor Rcor2 orchestrates neurogenesis in the developing mouse brain.
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.
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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, Beijing 100101, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: National Institute of Biological Sciences (NIBS), Beijing 102206, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Chenfei
authors.initials: C
authors.lastname: Wang
authors.affiliation: 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, Beijing 100101, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: 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, Beijing 100101, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Ding
authors.affiliation: 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, Beijing 100101, China.
authors.forename: Wensu
authors.initials: W
authors.lastname: Liu
authors.affiliation: 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, Beijing 100101, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Gao
authors.affiliation: 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, Beijing 100101, China.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D049109:Cell Proliferation; D056970:Co-Repressor Proteins; D005260:Female; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D056970:Co-Repressor Proteins; D009419:Nerve Tissue Proteins; C485650:Rcor2 protein, mouse; D012097:Repressor Proteins; D056466:Histone Demethylases; C504076:KDM1a protein, mouse