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(Circulation Research. 2008;102:12.)
© 2008 American Heart Association, Inc.

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Redundant Roles for Sox7 and Sox18 in Arteriovenous Specification in Zebrafish

Robert Herpers, Esther van de Kamp, Henricus J. Duckers^*, Stefan Schulte-Merker^*

From the Hubrecht Institute (R.H., S.S.-M.), Utrecht; and Molecular Cardiology Laboratory (R.H., E.v.d.K., H.J.D.), Experimental Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands.

Correspondence to Stefan Schulte-Merker, Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. E-mail s.schulte{at}niob.knaw.nl

The specification of arteries and veins is an essential process in establishing and maintaining a functional blood vessel system. Incorrect arteriovenous specification disrupts embryonic development but has also been diagnosed in human syndromes such as hypotrichosis–lymphedema–telangiectasia, characterized by defects in blood and lymphatic vessels and associated with mutations in SOX18. Here we characterize the role of sox7 and sox18 during zebrafish vasculogenesis. Sox7 and sox18 are specifically expressed in the developing vasculature, and simultaneous loss of their function results in a severe loss of the arterial identity of the presumptive aorta which instead expresses venous markers, followed by dramatic arteriovenous shunt formations. Our study identifies members of the Sox family as key factors in specifying arteriovenous identity and will help to better understand hypotrichosis–lymphedema–telangiectasia and other diseases.

Key Words: zebrafish • sox7 • sox18 • AV-differentiation • hypotrichosis–lymphedema–telangiectasia • hereditary hemorrhagic telangiectasia

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