Expression and function of c-Kit in fetal hemopoietic progenitor cells: transition from the early c-Kit-independent to the late c-Kit-dependent wave of hemopoiesis in the murine embryo.

The protooncogene c-kit encodes a receptor type tyrosine kinase and is allelic with the W locus of mice. SLF, the c-Kit ligand which is encoded by the Sl locus, has growth promoting activity for hemopoietic stem cells. Previous studies demonstrated that c-Kit is functionally required for the proliferation of hemopoietic progenitor cells at various differentiation stages in adult bone marrow. However, the absence of functional SLF and c-Kit in fetuses with mutant alleles of Sl and W loci produces only minor effects on the myeloid and early erythroid progenitor cells in the fetal liver, although the level of the late erythroid progenitor cells is significantly affected. We used an anti-c-Kit monoclonal antibody to investigate the expression and function of c-Kit in murine fetal hemopoietic progenitor cells. Flow-cytometric analysis showed that hemopoiesis in the yolk sac and fetal liver started from cells that express c-Kit. The c-Kit expression decreased upon maturation into erythrocytes in each organ. By fluorescence activated cell sorting, the c-Kit+ cell population was enriched with the hemopoietic progenitor cells clonable in vitro (CFU-E, BFU-E and GM-CFC). To elucidate whether c-Kit functions in these progenitor cells in vivo, we took advantage of the antagonistic anti-c-Kit monoclonal antibody, ACK2, which can block the function of c-Kit. Administration of ACK2 after 12.5 days of gestation rapidly eliminated BFU-E and GM-CFC as well as CFU-E from the fetal liver. However, the number of these progenitor cells in the yolk sac and fetal liver was less affected when the fetuses were given ACK2 before 12.5 days of gestation. Our results provide evidence that there are two waves of hemopoiesis in murine embryos relative to c-Kit dependency. The c-Kit has an essential role on the growth of hemopoietic progenitor cells in the fetal liver after 12.5 days of gestation, whereas the progenitor cells in the liver and yolk sac of the earlier embryo do not depend on c-Kit and its ligand SLF.

[1]  S. Nishikawa,et al.  Developmentally regulated cell surface expression and function of c-kit receptor during lymphocyte ontogeny in the embryo and adult mice. , 1992, Development.

[2]  H Ueno,et al.  The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. , 1992, Science.

[3]  D. Orlic,et al.  Stem cell factor increases colony-forming unit-spleen number in vitro in synergy with interleukin-6, and in vivo in Sl/Sld mice as a single factor. , 1992, Blood.

[4]  I. Weissman,et al.  Evidence that hematopoietic stem cells express mouse c-kit but do not depend on steel factor for their generation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[5]  D. van der Kooy,et al.  Contiguous patterns of c-kit and steel expression: analysis of mutations at the W and Sl loci. , 1991, Development.

[6]  N. Copeland,et al.  A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[7]  S. Nishikawa,et al.  Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function. , 1991, Development.

[8]  D. Birnbaum,et al.  Murine Flt3, a gene encoding a novel tyrosine kinase receptor of the PDGFR/CSF1R family. , 1991, Oncogene.

[9]  K. Zsebo,et al.  Enhancement of murine blast cell colony formation in culture by recombinant rat stem cell factor, ligand for c-kit. , 1991, Blood.

[10]  J. Adamson,et al.  Stem cell factor induces proliferation and differentiation of highly enriched murine hematopoietic cells. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S. Nishikawa,et al.  In utero manipulation of coat color formation by a monoclonal anti‐c‐kit antibody: two distinct waves of c‐kit‐dependency during melanocyte development. , 1991, The EMBO journal.

[12]  N. Nicola,et al.  Direct proliferative actions of stem cell factor on murine bone marrow cells in vitro: effects of combination with colony-stimulating factors. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[13]  S. Nishikawa,et al.  Expression and function of c-kit in hemopoietic progenitor cells , 1991, The Journal of experimental medicine.

[14]  D. Pardoll,et al.  A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populations , 1991, Cell.

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

[16]  R. Jaenisch,et al.  Migration and proliferation of cultured neural crest cells in W mutant neural crest chimeras. , 1991, Development.

[17]  D. Williams,et al.  The effect of recombinant mast cell growth factor on purified murine hematopoietic stem cells , 1991, The Journal of experimental medicine.

[18]  D. Williams,et al.  Influence of murine mast cell growth factor (c-kit ligand) on colony formation by mouse marrow hematopoietic progenitor cells. , 1991, Experimental hematology.

[19]  A. F. Wells,et al.  Cytokine Gene Expression: Analysis using Northern Blotting, Polymerase Chain Reaction and in situ Hybridization , 1991, Immunological reviews.

[20]  S. Nishikawa,et al.  Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule. , 1991, Blood.

[21]  B. Hogan,et al.  Embryonic expression of a haematopoietic growth factor encoded by the SI locus and the ligand for c-kit , 1990, Nature.

[22]  P. Leder,et al.  The hematopoietic growth factor KL is encoded by the SI locus and is the ligand of the c-kit receptor, the gene product of the W locus , 1990, Cell.

[23]  C. March,et al.  Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms , 1990, Cell.

[24]  David A. Williams,et al.  Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor , 1990, Cell.

[25]  K. Zsebo,et al.  Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver-conditioned medium , 1990, Cell.

[26]  N. Copeland,et al.  Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles , 1990, Cell.

[27]  P. Leder,et al.  The kit ligand: A cell surface molecule altered in steel mutant fibroblasts , 1990, Cell.

[28]  C. March,et al.  Identification of a ligand for the c-kit proto-oncogene , 1990, Cell.

[29]  K. Zsebo,et al.  Primary structure and functional expression of rat and human stem cell factor DNAs , 1990, Cell.

[30]  K. Nocka,et al.  Candidate ligand for the c‐kit transmembrane kinase receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors. , 1990, The EMBO journal.

[31]  I. Weissman,et al.  A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells , 1990, Cell.

[32]  Y. Yarden,et al.  Developmental expression of c-kit, a proto-oncogene encoded by the W locus. , 1990, Development.

[33]  S. Nishikawa,et al.  Stepwise progression of B lineage differentiation supported by interleukin 7 and other stromal cell molecules , 1990, The Journal of experimental medicine.

[34]  M. Shibuya,et al.  Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. , 1990, Oncogene.

[35]  S. Nishikawa,et al.  Interleukin 7 production and function in stromal cell-dependent B cell development , 1989, The Journal of experimental medicine.

[36]  A. Bernstein,et al.  Expression of c-kit gene products in known cellular targets of W mutations in normal and W mutant mice--evidence for an impaired c-kit kinase in mutant mice. , 1989, Genes & development.

[37]  Y. Kitamura,et al.  Heterogeneity of mast cells and phenotypic change between subpopulations. , 1989, Annual review of immunology.

[38]  D. Housman,et al.  The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene , 1988, Cell.

[39]  V. Chapman,et al.  The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus , 1988, Nature.

[40]  M. Ogawa,et al.  B cell ontogeny in murine embryo studied by a culture system with the monolayer of a stromal cell clone, ST2: B cell progenitor develops first in the embryonal body rather than in the yolk sac. , 1988, The EMBO journal.

[41]  F. Cormier,et al.  The wall of the chick embryo aorta harbours M-CFC, G-CFC, GM-CFC and BFU-E. , 1988, Development.

[42]  L. Sachs,et al.  Control of hematopoietic cell growth regulators during mouse fetal development , 1987, Molecular and cellular biology.

[43]  P. Hollands.  Differentiation and grafting of haemopoietic stem cells from early postimplantation mouse embryos. , 1987, Development.

[44]  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.

[45]  B. Mintz,et al.  Development of adult bone marrow stem cells in H-2-compatible and - incompatible mouse fetuses , 1984, The Journal of experimental medicine.

[46]  K. A. Wall,et al.  Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. , 1983, Journal of immunology.

[47]  Y. Kitamura,et al.  Presence of mast cell precursors in the yolk sac of mice. , 1983, Developmental biology.

[48]  J. E. Lenz.  Mast , 1983 .

[49]  H. Koyama,et al.  A new preadipose cell line derived from newborn mouse calvaria can promote the proliferation of pluripotent hemopoietic stem cells in vitro , 1982, Journal of cellular physiology.

[50]  R. A. Smith,et al.  "Hemogenic endothelium" of the embryonic aorta: Does it exist? , 1982, Developmental and comparative immunology.

[51]  D. Harrison,et al.  Processing by the thymus is not required for cells that cure and populate W/WV recipients , 1979 .

[52]  B. Mintz,et al.  Prevention of genetic anemias in mice by microinjection of normal hematopoietic stem cells into the fetal placenta. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[53]  G. Galfré,et al.  Mac‐1: a macrophage differentiation antigen identified by monoclonal antibody , 1979, European journal of immunology.

[54]  E. Russell.  Hereditary anemias of the mouse: a review for geneticists. , 1979, Advances in genetics.

[55]  D. Harrison,et al.  Processing by the thymus is not required for cells that cure and populate W/WV recipients. , 1979, Blood.

[56]  D. Chui,et al.  Fetal erythropoiesis in steel mutant mice. III. Defect in differentiation from BFU-E to CFU-E during early development. , 1978, Blood.

[57]  M. Feldman,et al.  In vitro activation of the in vivo colony‐forming units of the mouse yolk sac , 1977, Journal of cellular physiology.

[58]  F. Dieterlen-Lièvre,et al.  On the origin of haemopoietic stem cells in the avian embryo: an experimental approach. , 1975, Journal of embryology and experimental morphology.

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

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

[61]  F. Sieber,et al.  Erythroid colony formation in cultures of mouse and human bone marrow: Analysis of the requirement for erythropoietin by gel filtration and affinity chromatography on agarose‐concanavalin A , 1974, Journal of cellular physiology.

[62]  M. Moore,et al.  Ontogeny of the Haemopoietic System: Yolk Sac Origin of In Vivo and In Vitro Colony Forming Cells in the Developing Mouse Embryo * , 1970, British journal of haematology.

[63]  L. Herzenberg,et al.  Studies on the ontogeny of the mouse immune system. II. Immunoglobulin-producing cells. , 1968, Journal of immunology.

[64]  J. Barker.  Development of the mouse hematopoietic system. I. Types of hemoglobin produced in embryonic yolk sac and liver. , 1968, Developmental biology.

[65]  M. W. Thompson,et al.  Analysis of effects of W and f genic substitutions on fetal mouse hematology. , 1968, Genetics.