Submitted May 9, 2006
Accepted June 12, 2006
STAT5 acts as a repressor to regulate early embryonic
erythropoiesis
Matthew Schmerer, Ingrid Torregroza, Aude Pascal, Muriel Umbhauer, and Todd Evans*
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine
Laboratoire de Biologie du developpement, UMR7622, Universite Pierre et Marie Curie
* Corresponding author; email: tevans{at}aecom.yu.edu.
STAT5 regulates definitive (adult stage) erythropoiesis
through its ability to transduce signals from the
erythropoietin receptor. A function for STAT-dependent
signaling during primitive (embryonic) erythropoiesis has
not been analyzed. We tested this in the Xenopus system,
because STAT5 is expressed at the right time and place to
regulate development of the embryonic primitive ventral
blood island. Depletion of STAT5 activity results in
delayed accumulation of the first globin expressing cells,
indicating that the gene does regulate primitive
erythropoiesis. Our results suggest that in this context
STAT5 functions as a repressor, since forced expression of
an activator isoform blocks erythropoiesis, while embryos
expressing a repressor isoform develop normally. The
erythroid phenotype caused by the activator isoform of
STAT5 resembles that caused by over-expression of FGF. We
show that STAT5 isoforms can function epistatic to FGF and
can be phosphorylated in response to hyper-activated FGF
signaling in Xenopus embryos. Therefore, our data indicate
that STAT5 functions in both primitive and definitive
erythropoiesis, but by different mechanisms.
