title: CoREST/LSD1 control the development of pyramidal cortical neurons.
abstract: The development of a neuron from a precursor cell comprises a complex set of steps ranging from regulation of the proliferative cycle through the acquisition of distinct morphology and functionality. How these processes are orchestrated is largely unknown. Using in utero manipulation of gene expression in the mouse embryonic cerebral cortex, we found that the transition between multipolar and bipolar stages of newborn cortical pyramidal neurons is markedly delayed by depletion of CoREST, a corepressor component of chromatin remodeling complexes. This profoundly affects the onset of their radial migration. The loss of CoREST function also perturbs the dynamics of neuronal precursor cell populations, transiently increasing the fraction of cells remaining in progenitor states, but not the acquisition of the neuronal glutamatergic fate of pyramidal cells. The function of CoREST in these processes appears to be independent of its best-known interactor, the RE-1 silencer of transcription/neural restrictive silencing factor, and requires the histone demethylase LSD1. This reveals the importance of epigenetic control in the execution of neural development programs, specifically in the cerebral cortex.
authors: Program in Physiology and Biophysics, Institute for Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Independencia 1027, Santiago, Chile.
authors: Patricio
authors: P
authors: Fuentes
authors: José
authors: J
authors: Cánovas
authors: F Andrés
authors: FA
authors: Berndt
authors: Stephen C
authors: SC
authors: Noctor
authors: Manuel
authors: M
authors: Kukuljan
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology*; D056970:Co-Repressor Proteins; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D056466:Histone Demethylases; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010089:Oxidoreductases, N-Demethylating / Q000502:physiology*; D011247:Pregnancy; D017966:Pyramidal Cells / Q000196:embryology*; D012097:Repressor Proteins / Q000502:physiology*
chemical_list: C452880:Atp5md protein, rat; D056970:Co-Repressor Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C485650:Rcor2 protein, mouse; D012097:Repressor Proteins; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D010089:Oxidoreductases, N-Demethylating