title: p107 regulates neural precursor cells in the mammalian brain.
abstract: Here we show a novel function for Retinoblastoma family member, p107 in controlling stem cell expansion in the mammalian brain. Adult p107-null mice had elevated numbers of proliferating progenitor cells in their lateral ventricles. In vitro neurosphere assays revealed striking increases in the number of neurosphere forming cells from p107(-/-) brains that exhibited enhanced capacity for self-renewal. An expanded stem cell population in p107-deficient mice was shown in vivo by (a) increased numbers of slowly cycling cells in the lateral ventricles; and (b) accelerated rates of neural precursor repopulation after progenitor ablation. Notch1 was up-regulated in p107(-/-) neurospheres in vitro and brains in vivo. Chromatin immunoprecipitation and p107 overexpression suggest that p107 may modulate the Notch1 pathway. These results demonstrate a novel function for p107 that is distinct from Rb, which is to negatively regulate the number of neural stem cells in the developing and adult brain.
authors.affiliation: Neuroscience Research Group, Ottawa Health Research Institute, Ottawa, Ontario, Canada.
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Vanderluit
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Ferguson
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Nikoletopoulou
authors.forename: Maura
authors.initials: M
authors.lastname: Parker
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ruzhynsky
authors.forename: Tania
authors.initials: T
authors.lastname: Alexson
authors.forename: Stephen M
authors.initials: SM
authors.lastname: McNamara
authors.forename: David S
authors.initials: DS
authors.lastname: Park
authors.forename: Michael
authors.initials: M
authors.lastname: Rudnicki
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Slack
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch; D016160:Retinoblastoma Protein / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D016160:Retinoblastoma Protein; D001973:Bromodeoxyuridine