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M603226200v1
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Papers In Press, published online ahead of print May 16, 2006
J. Biol. Chem, 10.1074/jbc.M603226200
Submitted on April 5, 2006
Revised on May 12, 2006
Accepted on May 16, 2006

Absence of EMP leads to failure of erythroblast nuclear extrusion

Shivani Soni, Shashi Bala, Babette Gwynn, Kenneth E. Sahr, Luanne L. Peters, and Manjit Hanspal

Department of Medicine, Center for Cell Biology, St. Elizabeth's Medical Center, Boston, MA 02135

Corresponding Author: manjit_hanspal{at}cchcs.org

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.


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