RB regulates the production and the survival of newborn neurons in the embryonic and adult dentate gyrus.
In mammals, hippocampal dentate gyrus granule cells (DGCs) constitute a particular neuronal population produced both during embryogenesis and adult life, and play key roles in neural plasticity and memory. However, the molecular mechanisms regulating neurogenesis in the dentate lineage throughout development and adulthood are still not well understood. The Retinoblastoma protein (RB), a transcriptional repressor primarily involved in cell cycle control and cell death, plays crucial roles during cortical development but its function in the formation and maintenance of DGCs remains unknown. Here, we show that loss of RB during embryogenesis induces massive ectopic proliferation and delayed cell cycle exit of young DGCs specifically at late developmental stages but without affecting stem cells. This phenotype was partially counterbalanced by increased cell death. Similarly, during adulthood, loss of RB causes ectopic proliferation of newborn DGCs and dramatically impairs their survival. These results demonstrate a crucial role for RB in the generation and the survival of DGCs in the embryonic and the adult brain. © 2016 Wiley Periodicals, Inc.
Department of Cellular and Molecular Medicine, University of Ottawa Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.
Renaud
R
Vandenbosch
Department of Cellular and Molecular Medicine, University of Ottawa Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.
Alysen
A
Clark
Department of Cellular and Molecular Medicine, University of Ottawa Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.
Bensun C
BC
Fong
Department of Biology, American University of Beirut, Beirut, Lebanon.
Saad
S
Omais
Department of Biology, American University of Beirut, Beirut, Lebanon.
Carine
C
Jaafar
Department of Cellular and Molecular Medicine, University of Ottawa Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.
Delphie
D
Dugal-Tessier
Department of Cellular and Molecular Medicine, University of Ottawa Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.
Jagroop
J
Dhaliwal
Department of Cellular and Molecular Medicine, University of Ottawa Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.
Diane C
DC
Lagace
Department of Cellular and Molecular Medicine, University of Ottawa Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.
David S
DS
Park
Department of Biology, American University of Beirut, Beirut, Lebanon. rslack@uottawa.ca.
Noël
N
Ghanem
Department of Cellular and Molecular Medicine, University of Ottawa Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada. ng13@aub.edu.lb.
Ruth S
RS
Slack
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology* / Q000196:embryology*; D050687:E2F1 Transcription Factor / Q000172:deficiency / Q000235:genetics; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*
D050687:E2F1 Transcription Factor; D050699:E2F3 Transcription Factor; C493754:E2f1 protein, mouse; C490840:E2f3 protein, mouse; D051858:Forkhead Transcription Factors; C489565:Foxg1 protein, mouse; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D016160:Retinoblastoma Protein; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse
RB, adult neurogenesis; cell cycle; hippocampal development; survival