Absence of erythroblast macrophage protein (Emp) leads to failure of erythroblast nuclear extrusion.
In mammals, the functional unit for definitive erythropoiesis is the erythroblastic island, a multicellular structure composed of a central macrophage surrounded by developing erythroblasts. Erythroblast-macrophage interactions play a central role in the terminal maturation of erythroblasts, including enucleation. One possible mediator of this cell-cell interaction is the protein Emp (erythroblast macrophage protein). We used targeted gene inactivation to define the function of Emp during hematopoiesis. Emp null embryos die perinatally and show profound alterations in the hematopoietic system. A dramatic increase in the number of nucleated, immature erythrocytes is seen in the peripheral blood of Emp null fetuses. In the fetal liver virtually no erythroblastic islands are observed, and the number of F4/80-positive macrophages is substantially reduced. Those present lack cytoplasmic projections and are unable to interact with erythroblasts. Interestingly, wild type macrophages can bind Emp-deficient erythroblasts, but these erythroblasts do not extrude their nuclei, suggesting that Emp impacts enucleation in a cell autonomous fashion. Previous studies have implicated the actin cytoskeleton and its reorganization in both erythroblast enucleation as well as in macrophage development. We demonstrate that Emp associates with F-actin and that this interaction is important in the normal distribution of F-actin in both erythroblasts and macrophages. Thus, Emp appears to be required for erythroblast enucleation and in the development of the mature macrophages. The availability of an Emp null model provides a unique experimental system to study the enucleation process and to evaluate the function of macrophages in definitive erythropoiesis.
Soni
Shivani
S
Department of Medicine, Center for Cell Biology, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.
Bala
Shashi
S
Gwynn
Babette
B
Sahr
Kenneth E
KE
Peters
Luanne L
LL
Hanspal
Manjit
M
D000199:Actins / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics; D017931:DNA Primers; D004900:Erythroblasts / Q000166:cytology / Q000502:physiology; D004920:Erythropoiesis; D005804:Genes, Lethal; D005838:Genotype; D006579:Heterozygote; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D013234:Stem Cells / Q000502:physiology
D000199:Actins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D017931:DNA Primers; C513480:erythroblast macrophage protein, mouse