Purinergic signaling during rat embryonic development
Adenosine 5'-triphosphate (ATP) has been shown to be an important extracellular signaling molecule that mediates various physiological activities via the P2 (P2X and P2Y) receptors. However, information on the expression patterns of the P2 receptors during mammalian embryogenesis is limited. We therefore examined the expression patterns of different P2 receptor subtypes in rat embryos. In the hindbrain neural tube, the P2X3 receptor was transiently expressed at embryonic day E11 in the cranial motor neurons and the outgrowing axons. ATP significantly inhibited neurite outgrowth from neural tube explants. P2X3 receptors were also prominently expressed in sensory ganglia at this early stage and were coexpressed with P2X2 receptors in El6.5 embryos. Other P2X receptor subtypes were observed in different brain regions such as subventricular zones, the site of postnatal neurogenesis. In addition, the P2Y receptor expression was detected in the somites and subsequently in the developing skeletal muscle but was downregulated as development proceeded. While the P2Y1 receptor was no longer expressed in the adult skeletal muscle, the expression of P2Y2 receptor was present, although restricted in the satellite cells and the P2Y4 receptor showed reduced expression in adult skeletal muscle. Likewise, the expression of the P2Y receptors was initially expressed throughout the myocardium (El2) but was gradually restricted to the trabeculated myocardium (El4-18). Studies on Ca2+ influx showed that particular P2 receptor subtypes of P2X2, P2X4, P2Y1, P2Y2, P2Y4 and P2Y6 receptors responded to nucleotides in E14 cardiomyocytes. P2X7 receptor expression was detected in developing pancreatic islet cells and later coexpressed with glucagon in ?-cells. In addition, transient expression of the P2X7 receptor in insulin-expressing cells was observed in the embryonic, but not in adult, islet cells. Together, the results indicated that widespread and dynamic expression of P2 receptors was found in the three-germ layer-derived embryonic tissues, particularly in some transient embryonic structures during development, which suggested they may be important in embryonic organogenesis.