ER71 Acts Downstream of BMP, Notch, and Wnt Signaling in Blood and Vessel Progenitor Specification

Dongjun Lee, Changwon Park, Ho Lee, Jesse J. Lugus, Seok Hyung Kim, Elizabeth Arentson, Yun Shin Chung, Gustavo Gomez, Michael Kyba, Shuo Lin, Ralf Janknecht, Dae Sik Lim, Kyunghee Choi

Research output: Contribution to journalArticlepeer-review

262 Scopus citations


FLK1-expressing (FLK1+) mesoderm generates blood and vessels. Here, we show that combined BMP, Notch, and Wnt signaling is necessary for efficient FLK1+ mesoderm formation from embryonic stem cells (ESCs). Inhibition of BMP, Notch, and Wnt signaling pathways greatly decreased the generation of FLK1+ mesoderm and expression of the Ets transcription factor Er71. Enforced expression of ER71 in ESCs resulted in a robust induction of FLK1+ mesoderm; rescued the generation of FLK1+ mesoderm when blocked by BMP, Notch, and Wnt inhibition; and enhanced hematopoietic and endothelial cell generation. Er71-deficient mice had greatly reduced FLK1 expression, died early in gestation, and displayed severe blood and vessel defects that are highly reminiscent of the Flk1 null mouse phenotype. Collectively, we provide compelling evidence that ER71 functions downstream of BMP, Notch, and Wnt signals and regulates FLK1+ mesoderm, blood, and vessel development.

Original languageEnglish (US)
Pages (from-to)497-507
Number of pages11
JournalCell Stem Cell
Issue number5
StatePublished - May 8 2008

Bibliographical note

Funding Information:
We thank Drs. G.Y. Koh, Y.Y. Kong, and Derek Persons for valuable materials, and we thank F. Long for helpful discussion. We also thank Drs. P. Jay and J.M. Kim for histological examinations. This work was supported by grants from the National Institutes of Health, NHLBI, HL63736 and HL55337 (K.C.), the 21st Century Frontier Functional Human Genome Project, NRL, Nuclear Research Programs of Korea (D.-S.L.), Korea National Cancer Center Control Program (H.L.), NIH, NIDDK, DK54508 (S.L.), the Mayo Foundation (R.J.), and by a predoctoral grant from the American Heart Association (J.J.L.). J.J.L. is a fellow of the Lucille P. Markey Pathway in Human Pathobiology.




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