Mechanisms and perspectives on differentiation of autonomic neurons

Neurons share many features in common but are distinguised by expression of phenotypic characteristics that define their specific function, location, or connectivity. One aspect of neuronal fate determination that has been extensively studied is that of neurotransmitter choice. The generation of diversity of neuronal subtypes within the developing nervous system involves integration of extrinsic and intrinsic instructive cues resulting in the expression of a core set of regulatory molecules. This review focuses on mechanisms of growth and transcription factor regulation in the generation of peripheral neural crest-derived neurons. Although the specification and differentiation of noradrenergic neurons are the focus, I have tried to integrate these into a larger picture providing a general roadmap for development of autonomic neurons. There is a core of DNA binding proteins required for the development of sympathetic, parasympathetic, and enteric neurons, including Phox2 and MASH1, whose specifity is regulated by the recruitment of additional transcriptional regulators in a subtype-specific manner. For noradrenergic neurons, the basic helix-loop-helix DNA binding protein HAND2 (dHAND) appears to serve this reveal a molecular mechanism to coordinate expression of pan-neuronal genes with cell type-specific genes. (C) 2004 Elsevier Inc. All rights reserved.