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Serotonergic transcriptional networks and potential importance to mental health

Nature Neuroscience volume 15, pages 519–527 (2012)Cite this article

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Abstract

Transcription regulatory networks governing the genesis, maturation and maintenance of vertebrate brain serotonin (5-HT) neurons determine the level of serotonergic gene expression and signaling throughout an animal's lifespan. Recent studies suggest that alterations in these networks can cause behavioral and physiological pathogenesis in mice. Here, we synthesize findings from vertebrate loss-of-function and gain-of-function studies to build a new model of the transcriptional regulatory networks that specify 5-HT neurons during fetal life, integrate them into CNS circuitry in early postnatal life and maintain them in adulthood. We then describe findings from animal and human genetic studies that support possible alterations in the activity of serotonergic regulatory networks in the etiology of mental illness. We conclude with a discussion of the potential utility of our model, as an experimentally well-defined molecular pathway, to predict and interpret the biological effect of genetic variation that may be discovered in the orthologous human network.

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Figure 1: Serotonergic neuron identity.
Figure 2: Neuroanatomical features of 5-HT neuron development.
Figure 3: Serotonergic progenitor specification.
Figure 4: Serotonergic transcription regulatory network.

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Acknowledgements

We thank R. Blakely (Vanderbilt University) and E. Gilmore (Case Western Reserve University) for valuable discussions and critical comments on the manuscript. Research in the Deneris Lab is supported by grants RO1 MH062723 and the Vanderbilt/NIMH Silvio O Conte Center for Neuroscience Research, P50 MH078028 from the US National Institutes of Health.

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  1. Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

    Evan S Deneris & Steven C Wyler

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Correspondence to Evan S Deneris.

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Deneris, E., Wyler, S. Serotonergic transcriptional networks and potential importance to mental health. Nat Neurosci 15, 519–527 (2012). https://doi.org/10.1038/nn.3039

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