Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins

Hannah L. Sunshine; Andrew C. Cicchetto; Karolina Elżbieta Kaczor-Urbanowicz; Feiyang Ma; Danielle Pi; Chloe Symons; Martin Turner; Vipul Shukla; Heather R. Christofk; Thomas A. Vallim; M. Luisa Iruela-Arispe

Cell Reports (Jan 2024)

Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins

Hannah L. Sunshine,
Andrew C. Cicchetto,
Karolina Elżbieta Kaczor-Urbanowicz,
Feiyang Ma,
Danielle Pi,
Chloe Symons,
Martin Turner,
Vipul Shukla,
Heather R. Christofk,
Thomas A. Vallim,
M. Luisa Iruela-Arispe

Affiliations

Hannah L. Sunshine: Molecular, Cellular, and Integrative Physiology Graduate Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Andrew C. Cicchetto: Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA
Karolina Elżbieta Kaczor-Urbanowicz: Center for Oral and Head/Neck Oncology Research, UCLA Biosystems & Function, UCLA School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095-1668, USA; UCLA Section of Orthodontics, UCLA School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA
Feiyang Ma: Department of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Danielle Pi: Department of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Chloe Symons: Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Martin Turner: Immunology Programme, The Babraham Institute, CB22 3AT Cambridge, UK
Vipul Shukla: Department of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Center for Human Immunobiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Heather R. Christofk: Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095-1606, USA
Thomas A. Vallim: Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095-1606, USA
M. Luisa Iruela-Arispe: Department of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 1
p. 113627

Abstract

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Summary: Vascular morphogenesis requires a delicate gradient of Notch signaling controlled, in part, by the distribution of ligands (Dll4 and Jagged1). How Jagged1 (JAG1) expression is compartmentalized in the vascular plexus remains unclear. Here, we show that Jag1 mRNA is a direct target of zinc-finger protein 36 (ZFP36), an RNA-binding protein involved in mRNA decay that we find robustly induced by vascular endothelial growth factor (VEGF). Endothelial cells lacking ZFP36 display high levels of JAG1 and increase angiogenic sprouting in vitro. Furthermore, mice lacking Zfp36 in endothelial cells display mispatterned and increased levels of JAG1 in the developing retinal vascular plexus. Abnormal levels of JAG1 at the sprouting front alters NOTCH1 signaling, increasing the number of tip cells, a phenotype that is rescued by imposing haploinsufficiency of Jag1. Our findings reveal an important feedforward loop whereby VEGF stimulates ZFP36, consequently suppressing Jag1 to enable adequate levels of Notch signaling during sprouting angiogenesis.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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