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We have recently identified a new G protein-coupled receptor, msr/apj, whose transcripts are detected in the endothelium of the primary blood vessels and the newly forming heart (Mech. Dev. 1999;84:199). Its expression during formation of the embryonic vasculature incited us to investigate whether expression of the receptor also increased during the formation of retinal vessels, which occurs postnatally in the mouse. Interestingly, msr/apj transcripts are indeed associated with the forming vessels and trace the centrifugal extension of the superficial vasculature. We also show that expression of the endogenous ligand apelin is upregulated at the leading edge of vessel formation.

We have recently identified a new G protein-coupled receptor, X-msr, whose expression is associated with the endothelial lineage in Xenopus laevis (Devic, E., Paquereau, L., Vernier, P., Knibiehler, B., Audigier, Y., 1996. Expression of a new G protein-coupled receptor X-msr is associated with an endothelial lineage in Xenopus laevis. Mech. Dev. 59, 129-140). Based on its structural analogy to the human orphan receptor APJ, we cloned the murine msr/apj receptor and analyzed its expression in developing tissues. As observed for X-msr, msr/apj transcripts are detected in the endothelium of the primary blood vessels and the forming heart. In addition, they are expressed in somites, limb bud and branchial arches. This expression pattern is distinct from that of the Flk1 gene and suggests that the msr/apj gene is expressed in a subpopulation of endothelial precursors and a mesenchymal population derived from paraaxial mesoderm.

Characterization of a new family of G protein-coupled receptors is reported. Expression of these receptors is associated with endothelial lineage. Cloning of the Xenope X-msr receptor allowed to show that embryonic expression of this receptor occurred in the heart and developing primary blood vessels. Furthermore, within these cardiovascular structures, expression was restricted to the endothelial layer. Because structural similarities with the human orphan receptor h-APJ were found, the msr/apj receptor was cloned in mice. This showed that embryonic expression of this receptor was also confirmed to endothelial precursors. Thus, this receptor is the orthological equivalent in mice to the amphibian receptor X-msr. Molecular phylogenesis studies showed that the X-msr, msr/apj, and h-APJ receptors shared considerable homology with two CXC chemokine receptors, namely LCR1, whose name was recently changed to CXCR4, and RDC1, which is structurally similar to the CXCR2 receptor. The human h-APJ receptor is a co-receptor for entry of the HIV into T cells, a property associated only with CXC chemokine receptors in the lymphocyte population. These data suggest that this new signaling system may participate in endothelial precursor migration during developmental angiogenesis and in endothelial cell migration and proliferation during neoangiogenesis in adults.

In order to determine whether G protein-coupled receptors play a role in early embryogenesis, we looked for cDNA fragments amplified between primers located in consensus sequences of transmembrane segments. Using one such amplified fragment as a probe, we cloned a novel member of the G protein-coupled receptor superfamily in Xenopus. Alignment of the deduced protein sequence with that of other receptors discloses some homology with angiotensin receptors. A single transcript of 2.5 kb is detected at the late blastula stage and its expression increases during gastrulation. In situ hybridization reveals transcripts initially in the ventrolateral involuting marginal zone and later in the lateral plate mesoderm. At larval stages, the transcript is expressed in procardiac tube and forming blood vessels, where it is localized in the inner endothelial layer. Thus, this gene traces an endothelial lineage and represents a very early and unique marker in Xenopus of the specification of cardiac and vascular endothelia. We propose the name of X-msr for mesenchyme-associated serpentine receptor.