Negative and Positive Regulation of Erythropoiesis

Shuo Lin
Institute of Molecular Medicine and Genetics
Medical College of Georgia
Augusta, GA 30912
telephone: 706-721-8762
fax: 706-721-8752
prestype: Platform
presenter: Shuo Lin

The production of red blood cells is under both positive and negative control. Dysregulation of either of these may cause human diseases such as anemia or leukemia. Identification of lineage-specific regulators involved in erythroid cell proliferation should help elucidate the molecular basis underlying these diseases. We have performed a large-scale expression screen using a cDNA library constructed from the GATA-1 positive embryonic hematopoietic cells of transgenic zebrafish and have isolated more than 50 genes that are specifically expressed in erythroid cells. A number of negative regulators including receptors, transcription factors, and enzymes of the MAP kinase pathway have been identified. We report that ZH-DR, a novel hematopoietic death receptor gene isolated from zebrafish embryonic erythroid progenitor cells, plays a critical role in regulating erythropoiesis. While overexpression of ZE-DR induced rapid apoptosis, transgenic zebrafish expressing a dominant negative form of ZE-DR produced an excess of red blood cells. This study provides the first in vivo model of erythroid dysregulation caused by the down-regulation of a lineage-specific death receptor. In addition, we will discuss another zebrafish gene that can enhance GATA-1 expression in transgenic zebrafish embryos. Our studies in zebrafish have revealed novel information regarding negative and positive regulation of erythropoiesis and should be useful for understanding the similar process in higher vertebrates.

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