Yolk sac-derived primitive erythroblasts enucleate during mammalian embryogenesis.

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 beta 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.

[1]  D. Chui,et al.  Foetal Erythropoiesis in Steel Mutant Mice , 1975, British journal of haematology.

[2]  M. Tavassoli.  Embryonic and fetal hemopoiesis: an overview. , 1991, Blood cells.

[3]  N. Bethlenfalvay,et al.  Fetal erythropoiesis. Maturation in megaloblastic (yolk sac) erythropoiesis in the C 57 B1-6J mouse. , 1970, Acta haematologica.

[4]  C. Begley,et al.  Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl gene. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[5]  D. Chui,et al.  Hemoglobin switching during murine embryonic development: evidence for two populations of embryonic erythropoietic progenitor cells. , 1986, Blood.

[6]  B. Deurs,et al.  The microtubule marginal band of mammalian red blood cells , 1973, Zeitschrift für Anatomie und Entwicklungsgeschichte.

[7]  Jeffrey Malik,et al.  Circulation is established in a stepwise pattern in the mammalian embryo. , 2003, Blood.

[8]  G. Ackerman,et al.  A phase and electron microscopic study of vasculogenesis and erythropoiesis in the yolk sac of the mouse , 1971, The Anatomical record.

[9]  E. Russell,et al.  Fetal erythropoiesis in steel mutant mice. I. A morphological study of erythroid cell development in fetal liver. , 1974, Developmental biology.

[10]  P. Marks,et al.  Erythroid cell development in fetal mice: ultrastructural characteristics and hemoglobin synthesis. , 1967, Journal of molecular biology.

[11]  H. Vogel,et al.  On the kinetics of erythroid cell differentiation in fetal mice. I. Microspectrophotometric determination of the hemoglobin content in erythroid cells during gestation , 1973, Journal of cellular physiology.

[12]  A. de la Chapelle,et al.  Differentiation of mammalian somatic cells: DNA and hemoglobin synthesis in fetal mouse yolk sac erythroid cells. , 1969, Proceedings of the National Academy of Sciences of the United States of America.

[13]  A. Copp,et al.  Death before birth: clues from gene knockouts and mutations. , 1995, Trends in genetics : TIG.

[14]  F. Grosveld,et al.  Mechanisms of developmental control of transcription in the murine alpha- and beta-globin loci. , 1999, Genes & development.

[15]  J. Gauldie,et al.  Hemoglobin ontogeny during normal mouse fetal development. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[16]  C. Eaves,et al.  Properties of the earliest clonogenic hemopoietic precursors to appear in the developing murine yolk sac. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Keller,et al.  A common precursor for primitive erythropoiesis and definitive haematopoiesis , 1997, Nature.

[18]  M. Craig,et al.  A DEVELOPMENTAL CHANGE IN HEMOGLOBINS CORRELATED WITH AN EMBRYONIC RED CELL POPULATION IN THE MOUSE. , 1964, Developmental biology.

[19]  E. Lazarides,et al.  Vimentin downregulation is an inherent feature of murine erythropoiesis and occurs independently of lineage. , 1990, Development.

[20]  Alexander A. Maximow,et al.  A Textbook of Histology , 1935, The Indian Medical Gazette.

[21]  S. Orkin,et al.  Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL , 1995, Nature.

[22]  H. Iwatsuki,et al.  Death process of primitive erythrocytes and phagocytosis by liver macrophages of the mouse embryo. , 1997, Kaibogaku zasshi. Journal of anatomy.

[23]  S. Koury,et al.  The cytoskeleton of isolated murine primitive erythrocytes , 1987, Cell and Tissue Research.

[24]  W. Cohen,et al.  Marginal bands in camel erythrocytes. , 1979, Journal of cell science.

[25]  W. Vainchenker,et al.  Alteration of vimentin intermediate filament expression during differentiation of human hemopoietic cells. , 1983, The EMBO journal.

[26]  S. Swerdlow,et al.  A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis , 1991, Cell.

[27]  G. Matsumura,et al.  Haemopoietic cells of yolk sac and liver in the mouse embryo: a light and electron microscopical study. , 1986, Journal of anatomy.

[28]  A. Maximow.  Untersuchungen über Blut und Bindegewebe , 1908 .

[29]  Matthew H. Kaufman,et al.  The Atlas of Mouse Development , 1992 .

[30]  M. Monk.  Mammalian Development: A Practical Approach , 1988, Development.

[31]  W. Cohen,et al.  The cytoskeletal system of nucleated erythrocytes. , 1991, International review of cytology.

[32]  A. de la Chapelle,et al.  Synthesis of embryonic hemoglobins during erythroid cell development in fetal mice. , 1969, The Journal of biological chemistry.

[33]  M. Lichtman.  The ultrastructure of the hemopoietic environment of the marrow: a review. , 1981, Experimental hematology.

[34]  R. Steiner,et al.  On the kinetics of erythroid cell differentiation in fetal mice. III. DNA and hemoglobin measurements of individual erythroblasts during gestation , 1973, Journal of cellular physiology.

[35]  A. Maximow.  Untersuchungen über Blut und Bindegewebe , 1923 .

[36]  H. Takano-Ohmuro,et al.  The apoptotic and nonapoptotic nature of the terminal differentiation of erythroid cells. , 1998, Experimental Cell Research.

[37]  J. Palis,et al.  Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. , 1999, Development.

[38]  D. Turnbull,et al.  Onset of Cardiac Function During Early Mouse Embryogenesis Coincides With Entry of Primitive Erythroblasts Into the Embryo Proper , 2003, Circulation research.

[39]  Y Fujiwara,et al.  Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[40]  G. Stamatoyannopoulos,et al.  Cellular and molecular regulation of hemoglobin switching , 1979 .

[41]  E. Lazarides.  From genes to structural morphogenesis: The genesis and epigenesis of a red blood cell , 1987, Cell.

[42]  W. Cohen,et al.  The cytoskeletal system of mammalian primitive erythrocytes: studies in developing marsupials. , 1990, Cell motility and the cytoskeleton.

[43]  V. Ingram.  Embryonic Red Blood Cell Formation , 1972, Nature.

[44]  Dexter Tm,et al.  The essential cells of the hemopoietic microenvironment , 1984 .

[45]  J. Palis,et al.  Initiation of murine embryonic erythropoiesis: a spatial analysis. , 1997, Blood.