Purinergic signalling and development of the autonomic nervous system

Most early studies of the role of nucleotides in development have evidenced their crucial importance as carriers of energy in all organisms. However, an increasing number of studies are now available to suggest that purines and pyrimidines, acting as extracellular ligands specifically on receptors of the plasma membrane, may play a pivotal role throughout pre- and postnatal development in a wide variety of organisms including amphibians, birds, and mammals. Purinergic receptor expression and functions have been studied in the development of many organs, including the autonomic nervous system (ANS). Nucleotide receptors can induce a multiplicity of cellular signalling pathways via crosstalk with bioactive molecules acting on growth factors and neurotransmitter receptors which are fundamental for the development of a mature and functional ANS. Purines and pyrimidines may influence all the stages of neuronal development, including neural cell proliferation, migration, differentiation and phenotype determination of differentiated cells. Indeed, the normal development of the ANS is disturbed by dysfunction of purinergic signalling in animal models. To establish the primitive and fundamental nature of purinergic neurotransmission in the ontogeny of the ANS, in this review the roles of purines and pyrimidines as signalling molecules during embryological and postnatal development are considered.