Local guidance of emerging vessel sprouts requires soluble Flt-1.

Full Abstract

Blood vessel networks form via sprouting of endothelial cells from parent vessels. Extrinsic cues guide sprouts after they leave the initiation site, but these cues are likely insufficient to regulate initial outward movement, and many embryonic vessel networks form in the absence of a strong extrinsic gradient. We hypothesized that nascent sprouts are guided by spatial cues produced along their own vessels, and that soluble Flt-1 (sFlt-1) participates in this guidance. Analysis of developing vessels with perturbed flt-1 function revealed misguided emerging sprouts, and transgenic sFlt-1 rescued sprout guidance parameters. sflt-1 activity in endothelial cells immediately adjacent to the emerging sprout significantly improved local sprout guidance. Thus, we propose that a vessel-intrinsic system initially guides emerging sprouts away from the parent vessel, utilizing spatially regulated expression of sFlt-1 in conjunction with exogenous VEGF-A. Local sprout guidance defects are predicted to contribute to vessel dysmorphogenesis during perturbed development and disease.

Author information

Author/s: Chappell, John C (JC); Taylor, Sarah M (SM); Ferrara, Napoleone (N); Bautch, Victoria L (VL);

Affiliation: Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Grants: F32HL95359 (Agency:NHLBI NIH HHS) ; HL43174 (Agency:NHLBI NIH HHS) ; HL86564 (Agency:NHLBI NIH HHS) ; T32CA9156 (Agency:NCI NIH HHS) ; T32HD46369 (Agency:NICHD NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Developmental cell (Dev Cell), published in United States. (Language: eng)

Reference: 2009-Sep; vol 17 (issue 3) : pp 377-86

Dates: Created 2009/09/17; Completed 2009/09/30;

PMID: 19758562, status: MEDLINE (last retrieved date: 9/30/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals
Blood Vessels - embryology
Cells, Cultured
Embryonic Stem Cells - cytology
Gene Expression Regulation, Developmental
Mice
Mice, Transgenic
Models, Biological

Models, Biological
Neovascularization, Physiologic
Phenotype
Retina - embryology
Retinal Vessels - embryology
Time Factors
Vascular Endothelial Growth Factor A - metabolism
Vascular Endothelial Growth Factor Receptor-1 - genetics; physiology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Vascular Endothelial Growth Factor A (0) ; Flt1 protein, mouse (EC 2.7.1.112) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.1.112)

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