{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:30:54Z","timestamp":1791246654198,"version":"4.1.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,5,27]]},"abstract":"<jats:p>\n                    Retinoblastoma (\n                    <jats:italic>Rb<\/jats:italic>\n                    )-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\n                    <jats:italic>Rb<\/jats:italic>\n                    -deficient embryos, accompanied  by reduced placental transport function. When these\n                    <jats:italic>Rb<\/jats:italic>\n                    <jats:sup>-<\/jats:sup>\n                    <jats:sup>\/<\/jats:sup>\n                    <jats:sup>-<\/jats:sup>\n                    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\n                    <jats:italic>Rb<\/jats:italic>\n                    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\n                    <jats:italic>Rb<\/jats:italic>\n                    <jats:sup>-<\/jats:sup>\n                    <jats:sup>\/<\/jats:sup>\n                    <jats:sup>-<\/jats:sup>\n                    animals, including the ectopic apoptosis in the CNS, were virtually absent in  rescued\n                    <jats:italic>Rb<\/jats:italic>\n                    <jats:sup>-<\/jats:sup>\n                    <jats:sup>\/<\/jats:sup>\n                    <jats:sup>-<\/jats:sup>\n                    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\n                    <jats:italic>Rb<\/jats:italic>\n                    <jats:sup>-<\/jats:sup>\n                    <jats:sup>\/<\/jats:sup>\n                    <jats:sup>-<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1031853100","type":"journal-article","created":{"date-parts":[[2003,5,27]],"date-time":"2003-05-27T13:10:32Z","timestamp":1054041032000},"page":"6546-6551","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":116,"title":["<i>Rb<\/i>\n                    function in extraembryonic lineages suppresses apoptosis in  the CNS of\n                    <i>Rb<\/i>\n                    -deficient mice"],"prefix":"10.1073","volume":"100","author":[{"given":"Alain","family":"de Bruin","sequence":"first","affiliation":[{"name":"Human Cancer Genetics Program, Department of Molecular Virology, Immunology,  and Medical Genetics, Comprehensive Cancer Center, and Departments of Veterinary Biosciences, Molecular Genetics, and Pediatrics, Ohio State University, Columbus, OH 43210; and Division of Molecular and Human Genetics, Children's Research Institute,  Columbus, OH 43205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhao","family":"Wu","sequence":"additional","affiliation":[{"name":"Human Cancer Genetics Program, Department of Molecular Virology, Immunology,  and Medical Genetics, Comprehensive Cancer Center, and Departments of Veterinary Biosciences, Molecular Genetics, and Pediatrics, Ohio State University, Columbus, OH 43210; and Division of Molecular and Human Genetics, Children's Research Institute,  Columbus, OH 43205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold I.","family":"Saavedra","sequence":"additional","affiliation":[{"name":"Human Cancer Genetics Program, Department of Molecular Virology, Immunology,  and Medical Genetics, Comprehensive Cancer Center, and Departments of Veterinary Biosciences, Molecular Genetics, and Pediatrics, Ohio State University, Columbus, OH 43210; and Division of Molecular and Human Genetics, Children's Research Institute,  Columbus, OH 43205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Wilson","sequence":"additional","affiliation":[{"name":"Human Cancer Genetics Program, Department of Molecular Virology, Immunology,  and Medical Genetics, Comprehensive Cancer Center, and Departments of Veterinary Biosciences, Molecular Genetics, and Pediatrics, Ohio State University, Columbus, OH 43210; and Division of Molecular and Human Genetics, Children's Research Institute,  Columbus, OH 43205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Human Cancer Genetics Program, Department of Molecular Virology, Immunology,  and Medical Genetics, Comprehensive Cancer Center, and Departments of Veterinary Biosciences, Molecular Genetics, and Pediatrics, Ohio State University, Columbus, OH 43210; and Division of Molecular and Human Genetics, Children's Research Institute,  Columbus, OH 43205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Rosol","sequence":"additional","affiliation":[{"name":"Human Cancer Genetics Program, Department of Molecular Virology, Immunology,  and Medical Genetics, Comprehensive Cancer Center, and Departments of Veterinary Biosciences, Molecular Genetics, and Pediatrics, Ohio State University, Columbus, OH 43210; and Division of Molecular and Human Genetics, Children's Research Institute,  Columbus, OH 43205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Human Cancer Genetics Program, Department of Molecular Virology, Immunology,  and Medical Genetics, Comprehensive Cancer Center, and Departments of Veterinary Biosciences, Molecular Genetics, and Pediatrics, Ohio State University, Columbus, OH 43210; and Division of Molecular and Human Genetics, Children's Research Institute,  Columbus, OH 43205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Human Cancer Genetics Program, Department of Molecular Virology, Immunology,  and Medical Genetics, Comprehensive Cancer Center, and Departments of Veterinary Biosciences, Molecular Genetics, and Pediatrics, Ohio State University, Columbus, OH 43210; and Division of Molecular and Human Genetics, Children's Research Institute,  Columbus, OH 43205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Leone","sequence":"additional","affiliation":[{"name":"Human Cancer Genetics Program, Department of Molecular Virology, Immunology,  and Medical Genetics, Comprehensive Cancer Center, and Departments of Veterinary Biosciences, Molecular Genetics, and Pediatrics, Ohio State University, Columbus, OH 43210; and Division of Molecular and Human Genetics, Children's Research Institute,  Columbus, OH 43205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,5,5]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/323643a0"},{"key":"e_1_3_2_2_2","first-page":"43","volume":"1155","year":"1993","unstructured":"Goodrich, D. 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