FGFR-1 is required by epicardium-derived cells for myocardial invasion and correct coronary vascular lineage differentiation

Pennisi, D. J. and Mikawa, T (2009) FGFR-1 is required by epicardium-derived cells for myocardial invasion and correct coronary vascular lineage differentiation. Developmental Biology, 328 1: 148-159. doi:10.1016/j.ydbio.2009.01.023


Author Pennisi, D. J.
Mikawa, T
Title FGFR-1 is required by epicardium-derived cells for myocardial invasion and correct coronary vascular lineage differentiation
Journal name Developmental Biology   Check publisher's open access policy
ISSN 0012-1606
Publication date 2009-04
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.ydbio.2009.01.023
Open Access Status DOI
Volume 328
Issue 1
Start page 148
End page 159
Total pages 12
Editor R Krumlauf
Place of publication San Deigo, CA, U.S.A.
Publisher Academic Press
Collection year 2010
Language eng
Subject C1
970111 Expanding Knowledge in the Medical and Health Sciences
060103 Cell Development, Proliferation and Death
Abstract Critical steps in coronary vascular formation include the epithelial–mesenchyme transition (EMT) that epicardial cells undergo to become sub-epicardial; the invasion of the myocardium; and the differentiation of coronary lineages. However, the factors controlling these processes are not completely understood. Epicardial and coronary vascular precursors migrate to the avascular heart tube during embryogenesis via the proepicardium (PE). Here, we show that in the quail embryo fibroblast growth factor receptor (FGFR)-1 is expressed in a spatially and temporally restricted manner in the PE and epicardium-derived cells, including vascular endothelial precursors, and is up-regulated in epicardial cells after EMT. We used replication-defective retroviral vectors to over-express or knock-down FGFR-1 in the PE. FGFR-1 over-expression resulted in increased epicardial EMT. Knock-down of FGFR-1, however, did not inhibit epicardial EMT but greatly compromised the ability of PE progeny to invade the myocardium. The latter could, however, contribute to endothelia and smooth muscle of sub-epicardial vessels. Correct FGFR-1 levels were also important for correct coronary lineage differentiation with, at E12, an increase in the proportion of endothelial cells amongst FGFR-1 over-expressing PE progeny and a decrease in the proportion of smooth muscle cells in antisense FGFR-1 virus-infected PE progeny. Finally, in a heart explant system, constitutive activation of FGFR-1 signaling in epicardial cells resulted in increased delamination from the epicardium, invasion of the sub-epicardium, and invasion of the myocardium. These data reveal novel roles for FGFR-1 signaling in epicardial biology and coronary vascular lineage differentiation, and point to potential new therapeutic avenues.
Keyword Avian embryo
GROWTH-FACTOR RECEPTOR
Coronary vascular development
FGFR-1
Myocardial invasion
Epicardial EMT
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 03 Sep 2009, 08:31:58 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience