Extra-embryonic function of Rb is essential for embryonic development and viability

Lizhao Wu, Alain de Bruin, Harold I. Saavedra, Maja Starovic, Anthony Trimboli, Ying Yang, Jana Opavska, Pamela Wilson, John C. Thompson, Michael C. Ostrowski, Thomas J. Rosol, Laura A. Woollett, Michael Weinstein, James C. Cross, Michael L. Robinson and Gustavo Leone ()
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Lizhao Wu: The Ohio State University
Alain de Bruin: The Ohio State University
Harold I. Saavedra: The Ohio State University
Maja Starovic: University of Calgary Faculty of Medicine
Anthony Trimboli: The Ohio State University
Ying Yang: Children's Research Institute
Jana Opavska: The Ohio State University
Pamela Wilson: The Ohio State University
John C. Thompson: The Ohio State University
Michael C. Ostrowski: The Ohio State University
Thomas J. Rosol: The Ohio State University
Laura A. Woollett: University of Cincinnati Medical Center
Michael Weinstein: The Ohio State University
James C. Cross: University of Calgary Faculty of Medicine
Michael L. Robinson: The Ohio State University
Gustavo Leone: The Ohio State University

Nature, 2003, vol. 421, issue 6926, 942-947

Abstract: Abstract The retinoblastoma (Rb) gene was the first tumour suppressor identified1. Inactivation of Rb in mice results in unscheduled cell proliferation, apoptosis and widespread developmental defects, leading to embryonic death by day 14.5 (refs 2–4). However, the actual cause of the embryonic lethality has not been fully investigated. Here we show that loss of Rb leads to excessive proliferation of trophoblast cells and a severe disruption of the normal labyrinth architecture in the placenta. This is accompanied by a decrease in vascularization and a reduction in placental transport function. We used two complementary techniques—tetraploid aggregation and conditional knockout strategies—to demonstrate that Rb-deficient embryos supplied with a wild-type placenta can be carried to term, but die soon after birth. Most of the neurological and erythroid abnormalities thought to be responsible for the embryonic lethality of Rb-null animals were virtually absent in rescued Rb-null pups. These findings identify and define a key function of Rb in extra-embryonic cell lineages that is required for embryonic development and viability, and provide a mechanism for the cell autonomous versus non-cell autonomous roles of Rb in development.

Date: 2003
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DOI: 10.1038/nature01417

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