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First published online January 16, 2004
doi: 10.1242/10.1242/dev.00968

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SCL interacts with VEGF to suppress apoptosis at the onset of hematopoiesis

Richard Martin^1,2, Rachid Lahlil¹, Annette Damert^3,*, Lucile Miquerol^3,, Andras Nagy³, Gordon Keller⁴ and Trang Hoang^1,2,5,,

¹ Laboratory of Hematopoiesis and Leukemia, Clinical Research Institute of Montreal, Montreal, Canada
² Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Canada
³ Mount Sinai Hospital, Samuel Lunenfeld Research Institute, Toronto, Canada
⁴ Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, USA
⁵ Departments of Pharmacology, Biochemistry and Molecular Biology, University of Montreal, Montreal, Canada

Author for correspondence (e-mail: trang.hoang{at}umontreal.ca)

Accepted 28 October 2003

During development, hematopoiesis initiates in the yolk sac through a process that depends on VEGF/Flk1 signaling and on the function of the SCL/Tal1 transcription factor. Here we show that VEGF modifies the developmental potential of primitive erythroid progenitors and prolongs their life span. Furthermore, the survival of yolk sac erythrocytes in vivo depends on the dose of VEGF. Interestingly, in Vegf^lo/lo embryos carrying a hypomorph allele, Flk1-positive cells reach the yolk sac at E8.5, but are severely compromised in their ability to generate primitive erythroid precursors. These observations indicate that during embryonic development, different thresholds of VEGF are required for the migration and clonal expansion of hematopoietic precursors. The near absence of primitive erythroid precursors in Vegf^lo/lo embryos correlates with low levels of Scl in the yolk sac. Strikingly, gain-of-function of SCL partially complements the hematopoietic defect caused by the hypomorph Vegf^lo allele, and re-establishes the survival of erythroid cells and the expression of erythroid genes (Gata1 and ßH1). This indicates that SCL functions downstream of VEGF to ensure an expansion of the hematopoietic compartment.

Key words: VEGF, SCL, TAL1, Primitive erythropoiesis, Hematopoiesis, ES cell differentiation, Mouse

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