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Role of VEGF and tissue hypoxia in patterning of neural and vascular cells recruited to the embryonic heart
Author(s) -
Liu Hongbin,
Yang Qiwei,
Radhakrishnan Krishnan,
Whitfield Dedra E.,
Everhart Camille L. M.,
ParsonsWingerter Patricia,
Fisher Steven A.
Publication year - 2009
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22103
Subject(s) - biology , hypoxia (environmental) , embryonic stem cell , vasculogenesis , microbiology and biotechnology , neural stem cell , angiogenesis , anatomy , heart development , progenitor cell , medicine , cancer research , stem cell , oxygen , chemistry , biochemistry , organic chemistry , gene
Abstract We hypothesized that oxygen gradients and hypoxia‐responsive signaling may play a role in the patterning of neural or vascular cells recruited to the developing heart. Endothelial progenitor and neural cells are recruited to and form branched structures adjacent to the relatively hypoxic outflow tract (OFT) myocardium from stages 27–32 (ED6.5–7.5) of chick development. As determined by whole mount confocal microscopy, the neural and vascular structures were not anatomically associated. Adenoviral delivery of a VEGF trap dramatically affected the remodeling of the vascular plexus into a coronary tree while neuronal branching was normal. Both neuronal and vascular branching was diminished in the hearts of embryos incubated under hyperoxic conditions. Quantitative analysis of the vascular defects using our recently developed VESGEN program demonstrated reduced small vessel branching and increased vessel diameters. We propose that vascular and neural patterning in the developing heart share dependence on tissue oxygen gradients but are not interdependent. Developmental Dynamics 238:2760–2769, 2009. © 2009 Wiley‐Liss, Inc.