Journal
DEVELOPMENTAL DYNAMICS
Volume 240, Issue 2, Pages 384-393Publisher
WILEY-BLACKWELL
DOI: 10.1002/dvdy.22549
Keywords
CXCR7; G-protein coupled receptor; chemokine receptor; endocardial cells; cardiac valve remodeling; semilunar valve development; BMP signaling
Categories
Funding
- NHLBI NIH HHS [R01 HL057181-13, R01 HL080592-05, R01 HL080592-02, R01 HL062591-07, R01 HL057181-14, R01 HL062591-08, R01 HL080592-03, R01 HL080592, R01 HL057181, R01 HL080592-01, R01 HL057181-12, R01 HL080592-06, R01 HL062591, R01 HL062591-09, R01 HL057181-11, R01 HL080592-04] Funding Source: Medline
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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. Semi lunar 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(floxl-) 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. (C) 2011 Wiley-Liss, Inc.
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