Blood, 1 October 2002, Vol. 100, No. 7, pp. 2277-2277
Epo-EpoR signaling not required for cardiovascular or
neural development
Epo-EpoR signaling is required during definitive hematopoiesis
for the proliferation, survival, and differentiation of erythroid progenitors. In addition to its expression in hematopoietic cells, EpoR
is also expressed by endothelial cells, neural cells, and cardiac
tissue. But the requirement for Epo-EpoR signaling in these
nonhematopoietic tissues has remained unresolved. Both Epo- and EpoR-null mouse embryos have defects in
primitive hematopoiesis, cardiac formation, and blood vessel
development and die between embryonic day 13 (E13) and E15 due to
severe anemia. Until now, this prenatal lethality has precluded the
assessment of Epo-EpoR signaling in nonhematopoietic tissues.
To address the role of EpoR signaling in nonhematopoietic cells, Suzuki
and colleagues (page 2279) utilized a blood-specific regulatory element
of the GATA-1 promoter to drive expression of
EpoR in the erythroid lineage of EpoR-deficient
mice. Their results demonstrate that the transgenic expression of
EpoR in hematopoietic tissues was capable of rescuing
viability, resulting in the birth of apparently normal, healthy, and
fertile mice. Not only were the defects in primitive and definitive
hematopoiesis that are normally associated with a loss of Epo signaling
restored, but the rescued mice displayed normal blood vessel formation
and cardiac development. Moreover, no gross neurologic symptoms were evident. These findings indicate that EpoR is not directly required for
the development of the brain or cardiovascular systems, but rather the
nonhematopoietic defects of Epo- and EpoR-null
embryos are secondary to a lack of blood circulation.
While Epo-EpoR signaling in nonhematopoietic tissues is dispensable for
viability, it remains to be determined whether there is a more subtle
requirement for EpoR in their development. These mice will be
invaluable for future studies aimed at investigating the role of
Epo-EpoR signaling in response to stressful conditions such as
hypoxia and ischemia.
Noëlle Paffett-Lugassy and Leonard I. Zon
Harvard Institutes of
Medicine
