NDLI: Rb function in extraembryonic lineages suppresses apoptosis in the CNS of Rb-deficient mice.

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Rb function in extraembryonic lineages suppresses apoptosis in the CNS of Rb-deficient mice.

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Rb function in extraembryonic lineages suppresses apoptosis in the CNS of Rb-deficient mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Weinstein, Michael Wu, Lizhao Rosol, Thomas J. Yang, Ying De Bruin, Alain Wilson, Pamela Leone, Gustavo Saavedra, Harold I. Robinson, Michael L.
Description	Author Affiliation: de Bruin A ( Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus 43210, USA.);
Abstract	Retinoblastoma (Rb)-deficient embryos show severe defects in neurogenesis, erythropoiesis, and lens development and die at embryonic day 14.5. Our recent results demonstrated a drastic disorganization of the labyrinth layer in the placenta of Rb-deficient embryos, accompanied by reduced placental transport function. When these Rb-/- embryos were supplied with a wild-type placenta by using either tetraploid aggregation or genetic approaches, animals survived until birth. Here we analyze the role of extraembryonic Rb in regulating proliferation, apoptosis, and differentiation in the rescued animals at different developmental stages. Many of the neurological and erythroid abnormalities thought to be responsible for the embryonic lethality of Rb-/- animals, including the ectopic apoptosis in the CNS, were virtually absent in rescued Rb-/- pups. However, rescued animals died at birth with severe skeletal muscle defects. Like in Rb knockout embryos, rescued animals showed a marked increase in DNA replication and cell division in the CNS. In sharp contrast, the typical widespread neuronal apoptosis was absent in Rb-deficient embryos reconstituted with a normal placenta. In lens fiber cells, however, the inappropriate proliferation and apoptosis that is normally observed in Rb-/- embryos continued unabated in rescued animals. These results demonstrate that Rb function in extraembryonic lineages plays an important role in the survival of neuronal cells and in the differentiation of the erythroid lineage, providing mechanistic insight into the cell autonomous and nonautonomous functions of Rb during development.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Apoptosis Physiology Central Nervous System Cytology Retinoblastoma Protein Animals Immunohistochemistry Mice Mice, Knockout Mice, Transgenic Genetics Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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