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Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells

  1. Author:
    Stefater, J. A.
    Lewkowich, I.
    Rao, S.
    Mariggi, G.
    Carpenter, A. C.
    Burr, A. R.
    Fan, J. Q.
    Ajima, R.
    Molkentin, J. D.
    Williams, B. O.
    Wills-Karp, M.
    Pollard, J. W.
    Yamaguchi, T.
    Ferrara, N.
    Gerhardt, H.
    Lang, R. A.

  2. Author Address

    [Stefater, JA; Rao, S; Carpenter, AC; Fan, JQ; Lang, RA] Cincinnati Childrens Hosp, Visual Syst Grp, Div Pediat Ophthalmol, Med Ctr, Cincinnati, OH 45229 USA [Stefater, JA; Rao, S; Carpenter, AC; Fan, JQ; Lang, RA] Cincinnati Childrens Hosp, Div Dev Biol, Med Ctr, Cincinnati, OH 45229 USA [Stefater, JA; Rao, S] Univ Cincinnati, Dept Ophthalmol, Cincinnati, OH 45229 USA [Lewkowich, I; Wills-Karp, M] Cincinnati Childrens Hosp, Div Immunobiol, Med Ctr, Cincinnati, OH 45229 USA [Mariggi, G; Gerhardt, H] Canc Res UK, Vasc Biol Lab, London Res Inst, London WC2 3PX, England [Burr, AR; Molkentin, JD] Univ Cincinnati, Div Mol Cardiovasc Biol, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA [Ajima, R; Yamaguchi, T] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA [Molkentin, JD] Univ Cincinnati, Med Ctr, Howard Hughes Med Inst, Cincinnati Childrens Hosp, Cincinnati, OH 45229 USA [Williams, BO] Van Andel Res Inst, Ctr Skeletal Dis Res, Grand Rapids, MI 49503 USA [Pollard, JW] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY 10461 USA [Ferrara, N] Genentech Inc, San Francisco, CA 94080 USA [Gerhardt, H] VIB, Vasc Patterning Lab, Vesalius Res Ctr, B-3000 Louvain, Belgium;Lang, RA (reprint author), Cincinnati Childrens Hosp, Visual Syst Grp, Div Pediat Ophthalmol, Med Ctr, Cincinnati, OH 45229 USA;richard.lang@cchmc.org
    1. Year: 2011
    2. Date: Jun
  2. Journal: Nature
    1. 474
    2. 7352
    3. Pages: 511-U141
  4. Type of Article: Article
  5. ISSN: 0028-0836
  1. Abstract:

    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(1), somatic deletion in RMCs of the Wnt ligand transporter Wntless(2,3) 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)(4-6). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching.

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External Sources

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  2. DOI: 10.1038/nature10085
  3. View record in Web of Science®
  4. WOS: 000291939700049

Library Notes

  1. Fiscal Year: FY2010-2011
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