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Transcriptional regulation of arterial differentiation via Wnt, Sox and Notch

Morini, Marco Francescoa; Dejana, Elisabettaa,b

Current Opinion in Hematology: May 2014 - Volume 21 - Issue 3 - p 229–234
doi: 10.1097/MOH.0000000000000043
VASCULAR BIOLOGY: Edited by Thomas F. Deuel

Purpose of review: The development of a functionally and anatomically correct vascular network is a complex phenomenon that requires the combined activity of different signaling pathways and transcription factors. Notch signaling activation, for instance, is crucial for arterial specification. Here, we discuss the current knowledge on how other signaling pathways cooperate with Notch to orchestrate arterial differentiation of embryonic and postnatal vasculature.

Recent findings: The role of Notch in vascular development and arterial differentiation is well known. However, it was found that canonical Wnt signaling may act upstream of Notch, upregulating Dll4 and inducing endothelial cells to acquire arterial characteristics. Furthermore, the transcription factor Sox17 may act as a link between Wnt and Notch in the induction of a correct arterio/venous differentiation.

Summary: In the past years, the research on vascular development was mostly focused on the mechanisms that regulate vessel growth. We now understand that in order to interfere with several vascular diseases (e.g. aneurysm, cerebral ischemia and stroke) or tumor vascularization, we need to understand the signals that direct arterio/venous specification. Here, we discuss the interplay between Notch, Wnt and Sox that exert a combined positive action on arterial differentiation.

aIFOM, FIRC Institute of Molecular Oncology

bDepartment of Biosciences, University of Milan, Milan, Italy

Correspondence to Elisabetta Dejana, IFOM, FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy. Tel: +39 02574303234; e-mail:

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins