title: Cell-autonomous and non-cell-autonomous functions of the Rb tumor suppressor in developing central nervous system.
abstract: The retinoblastoma tumor suppressor (RB) plays an important role in the regulation of cell cycle progression and terminal differentiation of many cell types. Rb(-/-) mouse embryos die at midgestation with defects in cell cycle regulation, control of apoptosis and terminal differentiation. However, chimeric mice composed of wild-type and Rb-deficient cells are viable and show minor abnormalities. To determine the role of Rb in development more precisely, we analyzed chimeric embryos and adults made with marked Rb(-/-) cells. Like their germline Rb(-/-) counterparts, brains of midgestation chimeric embryos exhibited extensive ectopic S-phase entry. In Rb-mutants, this is accompanied by widespread apoptosis. However, in chimeras, the majority of Rb-deficient cells survived and differentiated into neuronal fates. Rescue of Rb(-/-) neurons in the presence of wild-type cells occurred after induction of the p53 pathway and led to accumulation of cells with 4n DNA content. Therefore, the role of Rb during development can be divided into a cell-autonomous function in exit from the cell cycle and a non-cell-autonomous role in the suppression of apoptosis and induction of differentiation.
authors: Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: M M
authors: MM
authors: Lipinski
authors: K F
authors: KF
authors: Macleod
authors: B O
authors: BO
authors: Williams
authors: T L
authors: TL
authors: Mullaney
authors: D
authors: D
authors: Crowley
authors: T
authors: T
authors: Jacks
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001921:Brain / Q000196:embryology / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D016923:Cell Death; D002454:Cell Differentiation; D002678:Chimera; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005260:Female; D005313:Fetal Death; D016161:Genes, Retinoblastoma; D005865:Gestational Age; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011247:Pregnancy; D016160:Retinoblastoma Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
chemical_list: D016160:Retinoblastoma Protein; D001616:beta-Galactosidase