Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins
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-f...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723016388 |
| _version_ | 1827395275651547136 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Hannah L. Sunshine |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T18:29:48Z |
| format | Article |
| id | doaj.art-7d029b8ee1744027bfa8881e01ccbc7e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-08T18:29:48Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7d029b8ee1744027bfa8881e01ccbc7e2023-12-30T04:44:13ZengElsevierCell Reports2211-12472024-01-01431113627Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteinsHannah L. Sunshine0Andrew C. Cicchetto1Karolina Elżbieta Kaczor-Urbanowicz2Feiyang Ma3Danielle Pi4Chloe Symons5Martin Turner6Vipul Shukla7Heather R. Christofk8Thomas A. Vallim9M. Luisa Iruela-Arispe10Molecular, 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, USADepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USACenter 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, USADepartment of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USADepartment of Cell and Development Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USARobert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USAImmunology Programme, The Babraham Institute, CB22 3AT Cambridge, UKDepartment 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, USADepartment 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, USADepartment 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, USADepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723016388CP: Cell biologyCP: Molecular biology |
| spellingShingle | 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 Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins Cell Reports CP: Cell biology CP: Molecular biology |
| title | Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins |
| title_full | Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins |
| title_fullStr | Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins |
| title_full_unstemmed | Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins |
| title_short | Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins |
| title_sort | endothelial jagged1 levels and distribution are post transcriptionally controlled by zfp36 decay proteins |
| topic | CP: Cell biology CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723016388 |
| work_keys_str_mv | AT hannahlsunshine endothelialjagged1levelsanddistributionareposttranscriptionallycontrolledbyzfp36decayproteins AT andrewccicchetto endothelialjagged1levelsanddistributionareposttranscriptionallycontrolledbyzfp36decayproteins AT karolinaelzbietakaczorurbanowicz endothelialjagged1levelsanddistributionareposttranscriptionallycontrolledbyzfp36decayproteins AT feiyangma endothelialjagged1levelsanddistributionareposttranscriptionallycontrolledbyzfp36decayproteins AT daniellepi endothelialjagged1levelsanddistributionareposttranscriptionallycontrolledbyzfp36decayproteins AT chloesymons endothelialjagged1levelsanddistributionareposttranscriptionallycontrolledbyzfp36decayproteins AT martinturner endothelialjagged1levelsanddistributionareposttranscriptionallycontrolledbyzfp36decayproteins AT vipulshukla endothelialjagged1levelsanddistributionareposttranscriptionallycontrolledbyzfp36decayproteins AT heatherrchristofk endothelialjagged1levelsanddistributionareposttranscriptionallycontrolledbyzfp36decayproteins AT thomasavallim endothelialjagged1levelsanddistributionareposttranscriptionallycontrolledbyzfp36decayproteins AT mluisairuelaarispe endothelialjagged1levelsanddistributionareposttranscriptionallycontrolledbyzfp36decayproteins |