» Articles » PMID: 16430858

Dll4-selective Notch Signaling Induces EphrinB2 Gene Expression in Endothelial Cells

Overview
Publisher Elsevier
Specialty Biochemistry
Date 2006 Jan 25
PMID 16430858
Citations 38
Authors
Affiliations
Soon will be listed here.
Abstract

The Notch pathway is involved in multiple aspects of vascular development, including arterial-venous differentiation. Here, we show that Notch stimulation instructively induces arterial characteristics in endothelial cells (EC). Forced expression of Notch intracellular domain (NICD, activated form of Notch) induced mRNA expression for a subset of arterial-specific markers such as ephrinB2, connexin40, and HERP1 only in EC but not other cell lines. In co-culture experiments using EC and either Dll4- or Jagged1-expressing cells, we found that Dll4 stimulation but not Jagged1 markedly induced ephrinB2 expression. An inducible expression of HERP1 and HERP2 by NICD has no measurable effects on expression of ephrinB2 and venous marker EphB4 although either HERP1 or HERP2 overexpression exerts potent inhibitory effects on EphB4 expression without ephrinB2 induction. We also found no functional interaction between Notch and TGF-beta-ALK1 signalings in an induction of ephrinB2 expression. These results suggest that Dll4-stimulated Notch signaling induces a part of arterial characteristics only in EC via HERP-independent mechanism. Our data provide new insight into the molecular mechanism of ligand-selective Notch activation during differentiation of arterial EC.

Citing Articles

The role of vascular and lymphatic networks in bone and joint homeostasis and pathology.

Huang J, Liao C, Yang J, Zhang L Front Endocrinol (Lausanne). 2024; 15:1465816.

PMID: 39324127 PMC: 11422228. DOI: 10.3389/fendo.2024.1465816.


Notch signaling regulates UNC5B to suppress endothelial proliferation, migration, junction activity, and retinal plexus branching.

Raza Q, Nadeem T, Youn S, Swaminathan B, Gupta A, Sargis T Sci Rep. 2024; 14(1):13603.

PMID: 38866944 PMC: 11169293. DOI: 10.1038/s41598-024-64375-z.


Eph-ephrin signaling couples endothelial cell sorting and arterial specification.

Stewen J, Kruse K, Godoi-Filip A, Zenia , Jeong H, Adams S Nat Commun. 2024; 15(1):2539.

PMID: 38570531 PMC: 10991410. DOI: 10.1038/s41467-024-46300-0.


Brain arteriovenous malformation in hereditary hemorrhagic telangiectasia: Recent advances in cellular and molecular mechanisms.

Drape E, Anquetil T, Larrivee B, Dubrac A Front Hum Neurosci. 2022; 16:1006115.

PMID: 36504622 PMC: 9729275. DOI: 10.3389/fnhum.2022.1006115.


Endothelial cell cycle state determines propensity for arterial-venous fate.

Chavkin N, Genet G, Poulet M, Jeffery E, Marziano C, Genet N Nat Commun. 2022; 13(1):5891.

PMID: 36202789 PMC: 9537338. DOI: 10.1038/s41467-022-33324-7.