Serotonin is a major signaling molecule produced in different parts of the body. In the brain serotonin is made by a very small number of neurons but it modulates a very diverse set of brain functions from biological rhythms to cognitive performance and brain plasticity. Serotonin’s effects on mood are the best known, because drugs increasing serotonin signaling are potent antidepressants. In addition altered serotonin signaling contributes to a wide range of neurological and psychiatric disorders including developmental disorders. Thus, knowledge of how serotonin neurons are specified during development and how they mature to reach all brain areas is an important step in our understanding of these disorders.
Figure illustrates the developing serotonin neurons in the brain of a mouse embryo aged 12 days. Serotonin neurons were stained in red with antibodies and visualized in 3D after tissue clearing. The rostral and caudal serotonin cell clusters are already formed and have distinct projections to the forebrain and brainstem respectively.
Recent progress in this area has lead researchers to realize that development of serotonin neurons is a multiple step operation that begins during early embryonic life when serotonin neurons are born but that it continues during a large part of postnatal life and even to some extent in adult life. It is now clear that serotonin neurons are highly plastic; their development, maturation and regeneration is controlled by a complex gene regulatory network in constant interaction with the environment.
In addition, researchers have come to realize that there is not one central serotonin system but many different serotonin subsystems that vary by localization, structural organization and molecular composition. Gene regulatory networks that control serotonin identity and their diversity have been elucidated. Importantly the gene regulatory networks that control 5-HT identity are needed throughout life to maintain serotonin neurotransmission identity and neuronal structure. Many molecules have been identified that contribute to the final position of serotonin neurons in the brain by controlling their migration and their correct wiring in defined neural circuits through the action of axon guidance molecules. An overview article recently published in WIREs Developmental Biology offers an updated view of these fundamental developmental mechanisms, pointing to the many ways by which developmental dysfunction of serotonin systems might occur at different periods in life. This opens new possibilities for therapeutic intervention, which can range from prevention of risk to stem cell therapies.
Kindly contributed by Evan Deneris and Patricia Gaspar.
