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Cited by 367

The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.

Erythropoietin receptor signalling is required for normal brain development

Yu, Xiaobing, Shacka, John J., Eells, Jeffrey B., Suarez-Quian, Carlos, Przygodzki, Ronald M., Beleslin-Cokic, Bojana, Lin, Chyuan-Sheng, Nikodem, Vera M., Hempstead, Barbara, Flanders, Kathleen C., Costantini, Frank, Noguchi, Constance Tom·2002·Development
DOI 10.1242/dev.129.2.505
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Abstract

Erythropoietin, known for its role in erythroid differentiation, has been shown to be neuroprotective during brain ischaemia in adult animal models. Although high levels of erythropoietin receptor are produced in embryonic brain, the role of erythropoietin during brain development is uncertain. We now provide evidence that erythropoietin acts to stimulate neural progenitor cells and to prevent apoptosis in the embryonic brain. Mice lacking the erythropoietin receptor exhibit severe anaemia and defective cardiac development, and die at embryonic day 13.5 (E13.5). By E12.5, in addition to apoptosis in foetal liver, endocardium and myocardium, the erythropoietin receptor null mouse shows extensive apoptosis in foetal brain. Lack of erythropoietin receptor affects brain development as early as E10.5, resulting in a reduction in the number of neural progenitor cells and increased apoptosis. Corresponding in vitro cultures of cortical cells from Epor–/– mice also exhibited decreases in neuron generation compared with normal controls and increased sensitivity to low oxygen tension with no surviving neurons in Epor–/– cortical cultures after 24 hour exposure to hypoxia. The viability of primary Epor+/+ rodent embryonic cortical neurons was further increased by erythropoietin stimulation. Exposure of these cultures to hypoxia induced erythropoietin expression and a tenfold increase in erythropoietin receptor expression, increased cell survival and decreased apoptosis. Cultures of neuronal progenitor cells also exhibited a proliferative response to erythropoietin stimulation. These data demonstrate that the neuroprotective activity of erythropoietin is observed as early as E10.5 in the developing brain, and that induction of erythropoietin and its receptor by hypoxia may contribute to selective cell survival in the brain.

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Metadata

Authors
Yu, X., Shacka, J. J., Eells, J. B., Suarez-Quian, C., Przygodzki, R. M., Beleslin-Cokic, B., Lin, C.-S., Nikodem, V. M., Hempstead, B., Flanders, K. C., Costantini, F., & Noguchi, C. T.
Venue
Development
Publisher
The Company of Biologists
Published
2002-01-15
Volume
129
Issue
2
Pages
505-516
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.129.2.505
OpenAlex
W2168323957
Cited by
367
References
52
FWCI
11.13
Type
journal article
Language
en
Open access
closed

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