Publication Date:
2011-05-31
Description:
Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally, somatic deletion in RMCs of the Wnt ligand transporter Wntless results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214992/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214992/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stefater, James A 3rd -- Lewkowich, Ian -- Rao, Sujata -- Mariggi, Giovanni -- Carpenter, April C -- Burr, Adam R -- Fan, Jieqing -- Ajima, Rieko -- Molkentin, Jeffery D -- Williams, Bart O -- Wills-Karp, Marsha -- Pollard, Jeffrey W -- Yamaguchi, Terry -- Ferrara, Napoleone -- Gerhardt, Holger -- Lang, Richard A -- G1002033/Medical Research Council/United Kingdom -- R01 AR053293/AR/NIAMS NIH HHS/ -- R01 EY015766/EY/NEI NIH HHS/ -- R01 EY015766-05/EY/NEI NIH HHS/ -- Cancer Research UK/United Kingdom -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 May 29;474(7352):511-5. doi: 10.1038/nature10085.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Visual Systems Group, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21623369" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Blood Vessels/growth & development
;
Endothelial Cells/metabolism
;
Fibroblasts
;
Intracellular Signaling Peptides and Proteins/genetics/metabolism
;
LDL-Receptor Related Proteins/genetics/metabolism
;
Ligands
;
Low Density Lipoprotein Receptor-Related Protein-5
;
Mice
;
Myeloid Cells/*metabolism
;
Neovascularization, Physiologic/*physiology
;
Receptors, G-Protein-Coupled
;
Retina/*cytology
;
*Signal Transduction
;
Vascular Endothelial Growth Factor A/antagonists & inhibitors
;
Vascular Endothelial Growth Factor
;
Receptor-1/deficiency/genetics/*metabolism/secretion
;
Wnt Proteins/deficiency/genetics/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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