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Genes discovered that regulate blood stem cell development

Boston--Researchers at Children's Hospital Boston have isolated a gene responsible for making blood stem cells. The findings appear in today's issue of the journal Nature. The gene, called cdx4, is responsible for establishing the location of blood cell formation in the developing embryo. Cdx4 works by altering the expression of HOX genes, which are involved in making the body plan. Surprisingly, the authors found that overexpression of cdx4 in zebrafish embryos, or in mouse embryonic stem cells, induces the new production of early blood cells. "We have been searching for genes in the zebrafish that participate in making blood stem cells," according to lead author, Leonard Zon, MD., of Children's Hospital Boston. "Now that we have these genes, we are one step closer to growing more blood stem cells. This will be potentially useful for patients with severe congenital anemias or bone marrow transplantation for cancer," adds Zon.

Scientists studied a mutant that had a severe anemia because it had few blood stem cells, and also had a tail defect. The zebrafish mutants generally die within seven to ten days after fertilization. They discovered the mutation in the cdx4 gene, which is associated with the early blood deficiency as well as abnormal developmental patterning, including aberrant hox gene expression. When researchers injected the mutants with hox genes, such as hoxb7a and hoxa9a, it resulted in almost complete rescue of the deficient blood cells. Another hox gene, hoxb6b showed some improvement, but hoxb8a did not have any effect on the blood defect. Researchers believe this shows blood cell development is dependent on the proper expression of these hox genes, and that overexpression of these genes can reverse a fatal deficiency in these blood cells. "These zebrafish findings will allow us to better understand normal blood development, with the hopes of eventually developing more effective treatments for these devastating blood diso
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Contact: Mary-Ellen Shay or Cara Birrittieri
cara.birrittieri@tch.harvard.edu
617-355-6420
Children's Hospital Boston
18-Sep-2003


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