@article {1490441,
	title = {Sphingosine 1-Phosphate Receptor Signaling Establishes AP-1 Gradients to Allow for Retinal Endothelial Cell Specialization},
	journal = {Dev Cell},
	volume = {52},
	number = {6},
	year = {2020},
	month = {2020 Mar 23},
	pages = {779-793.e7},
	abstract = {Transcriptional mechanisms that drive angiogenesis and organotypic vascular endothelial cell specialization are poorly understood. Here, we show that retinal endothelial sphingosine 1-phosphate receptors (S1PRs), which restrain vascular endothelial growth factor (VEGF)-induced angiogenesis, spatially restrict expression of JunB, a member of the activator protein 1 (AP-1) family of transcription factors (TFs). Mechanistically, VEGF induces JunB expression at the sprouting vascular front while S1PR-dependent vascular endothelial (VE)-cadherin assembly suppresses JunB expression in the nascent vascular network, thus creating a gradient of this TF. Endothelial-specific JunB knockout mice showed diminished expression of neurovascular guidance genes and attenuated retinal vascular network progression. In addition, endothelial S1PR signaling is required for normal expression of β-catenin-dependent genes such as TCF/LEF1 and ZIC3 TFs, transporters, and junctional proteins. These results show that S1PR signaling restricts JunB function to the expanding vascular front, thus creating an AP-1 gradient and enabling organotypic endothelial cell specialization of the vascular network.},
	issn = {1878-1551},
	doi = {10.1016/j.devcel.2020.01.016},
	author = {Yanagida, Keisuke and Engelbrecht, Eric and Niaudet, Colin and Jung, Bongnam and Gaengel, Konstantin and Holton, Kristina and Swendeman, Steven and Liu, Catherine H and Levesque, Michel V and Kuo, Andrew and Fu, Zhongjie and Smith, Lois E H and Betsholtz, Christer and Hla, Timothy}
}
