Polycomb limits the neurogenic competence of neural precursor cells to promote astrogenic fate transition.
During neocortical development, neural precursor cells (NPCs, or neural stem cells) produce neurons first and astrocytes later. Although the timing of the fate switch from neurogenic to astrogenic is critical for determining the number of neurons, the mechanisms are not fully understood. Here, we show that the polycomb group complex (PcG) restricts neurogenic competence of NPCs and promotes the transition of NPC fate from neurogenic to astrogenic. Inactivation of PcG by knockout of the Ring1B or Ezh2 gene or Eed knockdown prolonged the neurogenic phase of NPCs and delayed the onset of the astrogenic phase. Moreover, PcG was found to repress the promoter of the proneural gene neurogenin1 in a developmental-stage-dependent manner. These results demonstrate a role of PcG: the temporal regulation of NPC fate.
Hirabayashi
Yusuke
Y
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
Suzki
Nao
N
Tsuboi
Masafumi
M
Endo
Takaho A
TA
Toyoda
Tetsuro
T
Shinga
Jun
J
Koseki
Haruhiko
H
Vidal
Miguel
M
Gotoh
Yukiko
Y
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000254:growth & development / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase; D009419:Nerve Tissue Proteins; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D044767:Ubiquitin-Protein Ligases; D051153:Wnt Proteins; C107275:Eed protein, mouse; C486336:Neurog1 protein, mouse; C498410:Ezh2 protein, mouse; C489841:RNF2 protein, human