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Development 128, 2301-2308 (2001)
© 2001 The Company of Biologists Limited

Primitive erythropoiesis in the Xenopus embryo: the synergistic role of LMO-2, SCL and GATA-binding proteins

Paul E. Mead1,*, Anne E. Deconinck1,2, Tara L. Huber1, Stuart H. Orkin1,2 and Leonard I. Zon1,2,{ddagger}

1 Division of Hematology/Oncology, Department of Pediatrics, Harvard Medical School,
2 Howard Hughes Medical Institute, Children’s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
* Present address: Department of Pathology, D4047C, St. Jude Children’s Research Hospital, Memphis, TN 38103, USA

{ddagger}Author for correspondence (e-mail: zon{at}rascal.med.harvard.edu)

Accepted March 26, 2001

Hematopoietic stem cells are derived from ventral mesoderm during vertebrate development. Gene targeting experiments in the mouse have demonstrated key roles for the basic helix-loop-helix transcription factor SCL and the GATA-binding protein GATA-1 in hematopoiesis. When overexpressed in Xenopus animal cap explants, SCL and GATA-1 are each capable of specifying mesoderm to become blood. Forced expression of either factor in whole embryos, however, does not lead to ectopic blood formation. This apparent paradox between animal cap assays and whole embryo phenotype has led to the hypothesis that additional factors are involved in specifying hematopoietic mesoderm. SCL and GATA-1 interact in a transcriptional complex with the LIM domain protein LMO-2. We have cloned the Xenopus homolog of LMO-2 and show that it is expressed in a similar pattern to SCL during development. LMO-2 can specify hematopoietic mesoderm in animal cap assays. SCL and LMO-2 act synergistically to expand the blood island when overexpressed in whole embryos. Furthermore, co-expression of GATA-1 with SCL and LMO-2 leads to embryos that are ventralized and have blood throughout the dorsal-ventral axis. The synergistic effect of SCL, LMO-2 and GATA-1, taken together with the findings that these factors can form a complex in vitro, suggests that this complex specifies mesoderm to become blood during embryogenesis.

Key words: Xenopus, LMO-2, SCL, GATA-binding factors, Hematopoiesis




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© The Company of Biologists Ltd 2001