Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo

Denise Stenzel; Claudio A. Franco; Soline Estrach; Amel Mettouchi; Dominique Sauvaget; Ian Rosewell; Andreas Schertel; Hannah Armer; Anna Domogatskaya; Sergey Rodin; Karl Tryggvason; Lucy Collinson; Lydia Sorokin; Holger Gerhardt

doi:10.1038/embor.2011.194

Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo

Denise Stenzel^*, Claudio A. Franco, Soline Estrach, Amel Mettouchi, Dominique Sauvaget, Ian Rosewell, Andreas Schertel, Hannah Armer, Anna Domogatskaya, Sergey Rodin, Karl Tryggvason, Lucy Collinson, Lydia Sorokin, Holger Gerhardt

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

114 Citations (Scopus)

Abstract

How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin α4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo. Lama4 deficiency leads to reduced Dll4 expression, excessive filopodia and tip cell formation in the mouse retina, phenocopying the effects of Dll4/Notch inhibition. Lama4-mediated Dll4 expression requires a combination of integrins in vitro and integrin β1 in vivo. We conclude that appropriate laminin/integrin-induced signalling is necessary to induce physiologically functional levels of Dll4 expression and regulate branching frequency during sprouting angiogenesis in vivo.

Original language	English
Pages (from-to)	1135-1143
Number of pages	9
Journal	EMBO Reports
Volume	12
Issue number	11
DOIs	https://doi.org/10.1038/embor.2011.194
Publication status	Published - Nov 2011
Externally published	Yes

Keywords

integrin
laminin
Notch signalling
sprouting angiogenesis
vascular basement membrane

Access to Document

10.1038/embor.2011.194

Cite this

Stenzel, D., Franco, C. A., Estrach, S., Mettouchi, A., Sauvaget, D., Rosewell, I., Schertel, A., Armer, H., Domogatskaya, A., Rodin, S., Tryggvason, K., Collinson, L., Sorokin, L., & Gerhardt, H. (2011). Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo. EMBO Reports, 12(11), 1135-1143. https://doi.org/10.1038/embor.2011.194

@article{de16054e0cb64008b67533d3146afc75,

title = "Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo",

abstract = "How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin α4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo. Lama4 deficiency leads to reduced Dll4 expression, excessive filopodia and tip cell formation in the mouse retina, phenocopying the effects of Dll4/Notch inhibition. Lama4-mediated Dll4 expression requires a combination of integrins in vitro and integrin β1 in vivo. We conclude that appropriate laminin/integrin-induced signalling is necessary to induce physiologically functional levels of Dll4 expression and regulate branching frequency during sprouting angiogenesis in vivo.",

keywords = "integrin, laminin, Notch signalling, sprouting angiogenesis, vascular basement membrane",

author = "Denise Stenzel and Franco, {Claudio A.} and Soline Estrach and Amel Mettouchi and Dominique Sauvaget and Ian Rosewell and Andreas Schertel and Hannah Armer and Anna Domogatskaya and Sergey Rodin and Karl Tryggvason and Lucy Collinson and Lydia Sorokin and Holger Gerhardt",

year = "2011",

month = nov,

doi = "10.1038/embor.2011.194",

language = "English",

volume = "12",

pages = "1135--1143",

journal = "EMBO Reports",

issn = "1469-221X",

publisher = "Wiley-Blackwell",

number = "11",

}

Stenzel, D, Franco, CA, Estrach, S, Mettouchi, A, Sauvaget, D, Rosewell, I, Schertel, A, Armer, H, Domogatskaya, A, Rodin, S, Tryggvason, K, Collinson, L, Sorokin, L & Gerhardt, H 2011, 'Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo', EMBO Reports, vol. 12, no. 11, pp. 1135-1143. https://doi.org/10.1038/embor.2011.194

TY - JOUR

T1 - Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo

AU - Stenzel, Denise

AU - Franco, Claudio A.

AU - Estrach, Soline

AU - Mettouchi, Amel

AU - Sauvaget, Dominique

AU - Rosewell, Ian

AU - Schertel, Andreas

AU - Armer, Hannah

AU - Domogatskaya, Anna

AU - Rodin, Sergey

AU - Tryggvason, Karl

AU - Collinson, Lucy

AU - Sorokin, Lydia

AU - Gerhardt, Holger

PY - 2011/11

Y1 - 2011/11

N2 - How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin α4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo. Lama4 deficiency leads to reduced Dll4 expression, excessive filopodia and tip cell formation in the mouse retina, phenocopying the effects of Dll4/Notch inhibition. Lama4-mediated Dll4 expression requires a combination of integrins in vitro and integrin β1 in vivo. We conclude that appropriate laminin/integrin-induced signalling is necessary to induce physiologically functional levels of Dll4 expression and regulate branching frequency during sprouting angiogenesis in vivo.

AB - How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin α4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo. Lama4 deficiency leads to reduced Dll4 expression, excessive filopodia and tip cell formation in the mouse retina, phenocopying the effects of Dll4/Notch inhibition. Lama4-mediated Dll4 expression requires a combination of integrins in vitro and integrin β1 in vivo. We conclude that appropriate laminin/integrin-induced signalling is necessary to induce physiologically functional levels of Dll4 expression and regulate branching frequency during sprouting angiogenesis in vivo.

KW - integrin

KW - laminin

KW - Notch signalling

KW - sprouting angiogenesis

KW - vascular basement membrane

UR - http://www.scopus.com/inward/record.url?scp=80255135606&partnerID=8YFLogxK

U2 - 10.1038/embor.2011.194

DO - 10.1038/embor.2011.194

M3 - Article

C2 - 21979816

SN - 1469-221X

VL - 12

SP - 1135

EP - 1143

JO - EMBO Reports

JF - EMBO Reports

IS - 11

ER -

Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this