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Blood, 1 July 2004, Vol. 104, No. 1, pp. 19-25. Prepublished online as a Blood First Edition Paper on March 18, 2004; DOI 10.1182/blood-2003-12-4162. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4162v1 104/1/19    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kingsley, P. D. Articles by Palis, J. Search for Related Content PubMed PubMed Citation Articles by Kingsley, P. D. Articles by Palis, J. Related Collections Hematopoiesis and Stem Cells Red Cells Plenary Papers Free Research Articles Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPERS Yolk sac–derived primitive erythroblasts enucleate during mammalian embryogenesis Paul D. Kingsley, Jeffrey Malik, Katherine A. Fantauzzo, and James Palis From the Department of Pediatrics, Center for Human Genetics and Molecular Pediatric Disease, University of Rochester Medical Center, Rochester, NY. The enucleated definitive erythrocytes of mammals are unique in the animal kingdom. The observation that yolk sac–derived primitive erythroid cells in mammals circulate as nucleated cells has led to the conjecture that they are related to the red cells of fish, amphibians, and birds that remain nucleated throughout their life span. In mice, primitive red cells express both embryonic and adult hemoglobins, whereas definitive erythroblasts accumulate only adult hemoglobins. We investigated the terminal differentiation of murine primitive red cells with use of antibodies raised to embryonic H1-globin. Primitive erythroblasts progressively enucleate between embryonic days 12.5 and 16.5, generating mature primitive erythrocytes that are similar in size to their nucleated counterparts. These enucleated primitive erythrocytes circulate as late as 5 days after birth. The enucleation of primitive red cells in the mouse embryo has not previously been well recognized because it coincides with the emergence of exponentially expanding numbers of definitive erythrocytes from the fetal liver. Our studies establish a new paradigm in the understanding of primitive erythropoiesis and support the concept that primitive erythropoiesis in mice shares many similarities with definitive erythropoiesis of mammals. 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