Erythropoietin binding to erythropoitin receptor stimulates the proliferation of erythroid progenitor cells and globin production, and prevents apoptosis as cells differentiate along the erythroid pathway. Erythropoietin receptor expression is developmentally regulated as are the sites of hematopoiesis. Unexpectedly, erythropoietin receptor expression is also detected in embryonic and adult brain, placenta and vascular endothelium. We have detected high level of erythropoietin receptor expression in mouse embryonic day 9.5 neural tube that may be the origin of erythropoietin receptor brain transcripts which is down regulated later in development. An 80 kb human erythropoietin receptor genomic DNA fragment is able to recapitulate the general pattern of endogenous erythropoietin receptor expression in transgenic mice. As with the endogenous gene, this transgene is also inducible in hematopoietic tissue and brain by induced anemic stress. We find that the human transgene and mouse erythropoietin receptor gene contain common regulatory elements to direct appropriate expression in embryonic and adult hematopoietic tissue, and that transcription induction of erythropoietin receptor in response to anemic stress may be similar in hematopoietic and non-hematopoietic tissue expressing the erythropoietin receptor gene. These data suggest that in addition to erythropoiesis, erythropoietin receptor may play a role in the development or of select non-hematopoietic tissue. DNA expression array technology is being used to identify and characterize genes responsive to erythropoietin receptor stimulation in hematopoietic and non-hematopoietic cells. These analyses focus on mRNA expressed before and after stimulation by erythropoietin using model systems such as the human erythroleukemia K562 or neuronal SH-SY5Y cell lines.