Premium
The chemokine receptor CXCR7 functions to regulate cardiac valve remodeling
Author(s) -
Yu Sangho,
Crawford Dianna,
Tsuchihashi Takatoshi,
Behrens Timothy W.,
Srivastava Deepak
Publication year - 2011
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.22549
Subject(s) - biology , mesenchymal stem cell , microbiology and biotechnology , receptor , chemokine receptor , phenotype , heart development , mesenchyme , medicine , embryonic stem cell , anatomy , chemokine , genetics , gene
CXCR7 (RDC1), a G‐protein‐coupled receptor with conserved motifs characteristic of chemokine receptors, is enriched in endocardial and cushion mesenchymal cells in developing hearts, but its function is unclear. Cxcr7 germline deletion resulted in perinatal lethality with complete penetrance. Mutant embryos exhibited aortic and pulmonary valve stenosis due to semilunar valve thickening, with occasional ventricular septal defects. Semilunar valve mesenchymal cell proliferation increased in mutants from embryonic day 14 onward, but the cell death rate remained unchanged. Cxcr7 mutant valves had increased levels of phosphorylated Smad1/5/8, indicating increased BMP signaling, which may partly explain the thickened valve leaflets. The hyperproliferative phenotype appeared to involve Cxcr7 function in endocardial cells and their mesenchymal derivatives, as Tie2‐Cre Cxcr7 flox /− mice had semilunar valve stenosis. Thus, CXCR7 is involved in semilunar valve development, possibly by regulating BMP signaling, and may contribute to aortic and pulmonary valve stenosis. Developmental Dynamics 240:384–393, 2011. © 2011 Wiley‐Liss, Inc.