Abstract
The purinergic system is one of the oldest cell-to-cell communication mechanisms and exhibits relevant functions in the regulation of the central nervous system (CNS) development. Amongst the components of the purinergic system, the ionotropic P2X7 receptor (P2X7R) stands out as a potential regulator of brain pathology and physiology. Thus, P2X7R is known to regulate crucial aspects of neuronal cell biology, including axonal elongation, path-finding, synapse formation and neuroprotection. Moreover, P2X7R modulates neuroinflammation and is posed as a therapeutic target in inflammatory, oncogenic and degenerative disorders. However, the lack of reliable technical and pharmacological approaches to detect this receptor represents a major hurdle in its study. Here, we took advantage of the P2rx7-EGFP reporter mouse, which expresses enhanced green fluorescence protein (EGFP) immediately downstream of the P2rx7 proximal promoter, to conduct a detailed study of its distribution. We performed a comprehensive analysis of the pattern of P2X7R expression in the brain of E18.5 mouse embryos revealing interesting areas within the CNS. Particularly, strong labelling was found in the septum, as well as along the entire neural roof plate zone of the brain, except chorioidal roof areas, but including specialized circumventricular roof formations, such as the subfornical and subcommissural organs (SFO; SCO). Moreover, our results reveal what seems a novel circumventricular organ, named by us postarcuate organ (PArcO). Furthermore, this study sheds light on the ongoing debate regarding the specific presence of P2X7R in neurons and may be of interest for the elucidation of additional roles of P2X7R in the idiosyncratic histologic development of the CNS and related systemic functions.
Highlights
The development of the mammalian central nervous system (CNS) is a complex and dynamic process that requires an accurately orchestrated sequence of genetic, environmental, and biochemical events
Prior to offering an exhaustive analysis of E18.5 embryonic P2xr7-enhanced green fluorescence protein (EGFP) reporter mice, we confirmed that the expression of P2X7 receptor (P2X7R) is readily detectable at early stages of CNS development
The correlation between mRNA and protein levels of P2X7R, as well as their associated reporter EGFP, was confirmed by western blot experiments, positive results being perceptible at embryonic day 9 and showing a significant presence at the stages selected for the present study (E18.5) (Fig. 3)
Summary
The development of the mammalian CNS is a complex and dynamic process that requires an accurately orchestrated sequence of genetic, environmental, and biochemical events. The generation of neural cells, i.e. neurons, astrocytes and oligodendrocytes, implies a precise and positionally differential control of crucial processes, such as cell proliferation, cell fate determination, migration, maturation, synapse formation, network implementation, and eventually, controlled apoptosis, to define the correct neuronal number and location. The control of these processes accounts for multiple mechanisms including extracellular signaling molecules. In the CNS, purinergic receptors regulate cell growth and migration during development, and as the CNS matures modulate glia–glia/neuron-glia interactions, mechanosensory transduction, and autonomic functions (Abbracchio et al 2009; Burnstock 2007a)
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