New Insights Into the Roles of Retinoic Acid Signaling in Nervous System Development and the Establishment of Neurotransmitter Systems.

Secreted chiefly from the underlying mesoderm, the morphogen retinoic acid (RA) is well known to contribute to the specification, patterning, and differentiation of neural progenitors in the developing vertebrate nervous system. Furthermore, RA influences the subtype identity and neurotransmitter phenotype of subsets of maturing neurons, although relatively little is known about how these functions are mediated. This review provides a comprehensive overview of the roles played by RA signaling during the formation of the central and peripheral nervous systems of vertebrates and highlights its effects on the differentiation of several neurotransmitter systems. In addition, the evolutionary history of the RA signaling system is discussed, revealing both conserved properties and alternate modes of RA action. It is proposed that comparative approaches should be employed systematically to expand our knowledge of the context-dependent cellular mechanisms controlled by the multifunctional signaling molecule RA.