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First published online 17 February 2004
doi: 10.1242/jcs.00969

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The bHLH TAL-1/SCL regulates endothelial cell migration and morphogenesis

¹ UMR 5535, Institut de Génétique Moléculaire, IFR122, 1919 Route de Mende
² INSERM U475, 99 rue Puech Villa, F 34000-Montpellier, France
³ UMR 5124, Institut de Génétique Moléculaire, IFR122, 1919 Route de Mende

^* Author for correspondence (e-mail: mathieu{at}igm.cnrs-mop.fr)

Accepted 31 October 2003

The basic helix-loop-helix tal-1 gene (or scl), known for its fundamental role in embryonic and adult hematopoiesis in vertebrates, is also required for embryonic vascular remodeling. In adults, TAL-1 protein is undetectable in quiescent endothelium but it is present in newly formed vessels including tumoral vasculature, indicating its involvement in angiogenesis. Here, we demonstrate that TAL-1 expression is tightly regulated during in vitro angiogenesis: it is low during the initial step of migration and is upregulated during formation of capillary-like structures. We investigated whether ectopic expression of either wild-type TAL-1 or a dominant-negative mutant lacking the DNA-binding domain (-bas) modulates the activity of human primary endothelial cells in the angiogenic processes of migration, proliferation and cell morphogenesis. Overexpression of either wild-type or -bas TAL-1 affected chemotactic migration of primary endothelial cells without modifying their proliferative properties. Ectopic expression of wild-type TAL-1 accelerated the formation of capillary-like structures in vitro and, in vivo, enhanced vascularisation in mice (Matrigel implants) associated with a general enlargement of capillary lumens. Importantly, transduction of the mutant bas completely impaired in vitro angiogenesis and strongly inhibited vascularisation in mice. Taken together, our data show that TAL-1 modulates the angiogenic response of endothelial cells by stimulating cell morphogenesis and by influencing their behavior in migration. This study highlights the importance of TAL-1 regulation in postnatal vascular remodeling and provides the first physiological evidence that links TAL-1 activity to endothelial cell morphogenic processes.

Key words: TAL-1/SCL, bHLH, Angiogenesis, Endothelial cells

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