The Wnt/β-catenin pathway is evolutionary conserved signaling system that regulates cell differentiation and organogenesis. We show that endothelial specific stabilization of Wnt/β-catenin signaling alters early vascular development in the embryo. The phenotype resembles that induced by upregulation of Notch signaling, including lack of vascular remodeling, altered elongation of the intersomitic vessels, defects in branching, and loss of venous identity. Both in vivo and in vitro data showthat β-catenin upregulates Dll4 transcription and strongly increases Notch signaling in the endothelium, leading to functional and morphological alterations. The functional consequences of β-catenin signaling depend on the stage of vascular development and are lost when a gain-of-function mutation is induced at a late stage of development or postnatally. Our findings establish a link between Wnt and Notch signaling in vascular development. We propose that early and sustained β-catenin signaling prevents correct endothelial cell differentiation, altering vascular remodeling and arteriovenous specification.
The Wnt/β-catenin pathway modulates vascular remodeling and specification by upregulating DII4/Notch signaling / M. Corada, D. Nyqvist, F. Orsenigo, A. Caprini, C. Giampietro, M.M. Taketo, M.L. Iruela Arispe, R.H. Adams, E. Dejana. - In: DEVELOPMENTAL CELL. - ISSN 1534-5807. - 18:6(2010), pp. 938-949. [10.1016/j.devcel.2010.05.006]
The Wnt/β-catenin pathway modulates vascular remodeling and specification by upregulating DII4/Notch signaling
C. Giampietro;E. Dejana
2010
Abstract
The Wnt/β-catenin pathway is evolutionary conserved signaling system that regulates cell differentiation and organogenesis. We show that endothelial specific stabilization of Wnt/β-catenin signaling alters early vascular development in the embryo. The phenotype resembles that induced by upregulation of Notch signaling, including lack of vascular remodeling, altered elongation of the intersomitic vessels, defects in branching, and loss of venous identity. Both in vivo and in vitro data showthat β-catenin upregulates Dll4 transcription and strongly increases Notch signaling in the endothelium, leading to functional and morphological alterations. The functional consequences of β-catenin signaling depend on the stage of vascular development and are lost when a gain-of-function mutation is induced at a late stage of development or postnatally. Our findings establish a link between Wnt and Notch signaling in vascular development. We propose that early and sustained β-catenin signaling prevents correct endothelial cell differentiation, altering vascular remodeling and arteriovenous specification.File | Dimensione | Formato | |
---|---|---|---|
CORADA_2010.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
3.09 MB
Formato
Adobe PDF
|
3.09 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.