Serotonin neuron development: shaping molecular and structural identities

The continuing fascination with serotonin (5‐hydroxytryptamine, 5‐HT) as a nervous system chemical messenger began with its discovery in the brains of mammals in 1953. Among the many reasons for this decades‐long interest is that the small numbers of neurons that make 5‐HT influence the excitability of neural circuits in nearly every region of the brain and spinal cord. A further reason is that 5‐HT dysfunction has been linked to a range of psychiatric and neurological disorders many of which have a neurodevelopmental component. This has led to intense interest in understanding 5‐HT neuron development with the aim of determining whether early alterations in their generation lead to brain disease susceptibility. Here, we present an overview of the neuroanatomical organization of vertebrate 5‐HT neurons, their neurogenesis, and prodigious axonal architectures, which enables the expansive reach of 5‐HT neuromodulation in the central nervous system. We review recent findings that have revealed the molecular basis for the tremendous diversity of 5‐HT neuron subtypes, the impact of environmental factors on 5‐HT neuron development, and how 5‐HT axons are topographically organized through disparate signaling pathways. We summarize studies of the gene regulatory networks that control the differentiation, maturation, and maintenance of 5‐HT neurons. These studies show that the regulatory factors controlling acquisition of 5‐HT‐type transmitter identity continue to play critical roles in the functional maturation and the maintenance of 5‐HT neurons. New insights are presented into how continuously expressed 5‐HT regulatory factors control 5‐HT neurons at different stages of life and how the regulatory networks themselves are maintained. WIREs Dev Biol 2018, 7:e301. doi: 10.1002/wdev.301 This article is categorized under: Nervous System Development > Vertebrates: General Principles Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Nervous System Development > Secondary: Vertebrates: Regional Development