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Abstract
Blood and vascular cells are generated during early embryogenesis from a common precursor, the hemangioblast. The stem cell leukemia gene (SCL/tal 1) encodes a basic helix-loop-helix transcription factor that is essential for the normal development of blood progenitors and blood vessels. We have previously characterized a panel of SCL enhancers including the +19 element, which directs expression to hematopoietic stem cells and endothelium. Here we demonstrate that SCL is expressed in bone primordia during embryonic development and in adult osteoblasts. Despite consistent expression in cells of the osteogenic lineage, SCL protein is not required for bone specification of embryonic stem cells. In transgenic mice, the SCL +19 core enhancer directed reporter gene expression to vascular smooth muscle and bone in addition to blood and endothelium. A 644-bp fragment containing the SCL +19 core enhancer was active in both blood and bone cell lines and was bound in vivo by a common array of Ets and GATA transcription factors. Taken together with the recent observation that a common progenitor can give rise to blood and bone cells, our results suggest that the SCL +19 enhancer targets a mesodermal progenitor capable of generating hematopoietic, vascular, and osteoblastic progeny.
We thank Catherine Porcher and Stuart Orkin for the SCL−/− and wild-type J1 ES cells. The MLO-Y4 cells and the 2TL242 anti-hSCL antibody were gifts from Linda Bonewald and Karen Pulford, respectively. We are grateful for the assistance given us by Liz Delaney and Aileen Smith with ES cell culture, Sandie Piltz and Paula Braker with animal husbandry, Sharyn Bord with histology, Dongrong Chen with in situ hybridization, and Ian Donaldson for the web link.
This work was supported by the Leukemia Research Fund and the Wellcome Trust. J.E.P. is a C. J. Martin/R. G. Menzies Fellow of the National Health and Medical Research Council of Australia.