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The developmental role of serotonin: news from mouse molecular genetics

The developmental role of serotonin: news from mouse molecular genetics A limited number of neurons are specified to become serotonergic during development. In the central nervous system, this involves a sequence of transcription factors, such as Nkx2.2, Lmx1 and Pet1, that specify the 5-HT cell lineage within a restricted region of the ventral mesencephalon. Synthesis of serotonin in the periphery involves a different isoform of tryptophan hydoxylase and possibly other specification pathways. A partial serotonergic phenotype is transiently observed during development in the limbic cortex, thalamus, hypothalamus, brainstem and peripheral sensory neurons. These neurons do not synthesize 5-HT but transiently express the high-affinity 5-HT transporter and the vesicular monoamine transporter, allowing them to capture and store 5-HT. Extinction of these transient expressions is controlled, in part, by thyroid hormones. Studies of several knockout mouse strains in which 5-HT metabolism is abnormal, such as monoamine oxidase A, serotonin transporter and vesicular monoamine transporter knockout mice, indicate that a tight control of 5-HT is required during the period of refinement of brain connections. This is exemplified by altered development of the primary somatosensory cortex, the retinal projections and the spinal respiratory centres in these mice. The processes that have been found to be controlled by 5-HT levels in these in vivo models are axonal and dendritic remodelling, neuronal survival and neurogenesis. Knockouts and conditional knockouts for the genes that encode specific 5-HT receptor subtypes indicate that different 5-HT receptors control different developmental processes. For instance, 5-HT1B receptors are involved in axon arbour remodelling, 5-HT2B receptors in cell survival and 5-HT1A receptors in adult neurogenesis. Disturbance of these processes during the perinatal period has important consequences for adult behaviour. Investigations of genetic models with 5-HT target molecules provide interesting perspectives on developmental changes in the physiology of several psychiatric disorders. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Reviews Neuroscience Springer Journals

The developmental role of serotonin: news from mouse molecular genetics

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References (153)

Publisher
Springer Journals
Copyright
Copyright © 2003 by Nature Publishing Group
Subject
Biomedicine; Biomedicine, general; Neurosciences; Behavioral Sciences; Biological Techniques; Neurobiology; Animal Genetics and Genomics
ISSN
1471-003X
eISSN
1471-0048
DOI
10.1038/nrn1256
Publisher site
See Article on Publisher Site

Abstract

A limited number of neurons are specified to become serotonergic during development. In the central nervous system, this involves a sequence of transcription factors, such as Nkx2.2, Lmx1 and Pet1, that specify the 5-HT cell lineage within a restricted region of the ventral mesencephalon. Synthesis of serotonin in the periphery involves a different isoform of tryptophan hydoxylase and possibly other specification pathways. A partial serotonergic phenotype is transiently observed during development in the limbic cortex, thalamus, hypothalamus, brainstem and peripheral sensory neurons. These neurons do not synthesize 5-HT but transiently express the high-affinity 5-HT transporter and the vesicular monoamine transporter, allowing them to capture and store 5-HT. Extinction of these transient expressions is controlled, in part, by thyroid hormones. Studies of several knockout mouse strains in which 5-HT metabolism is abnormal, such as monoamine oxidase A, serotonin transporter and vesicular monoamine transporter knockout mice, indicate that a tight control of 5-HT is required during the period of refinement of brain connections. This is exemplified by altered development of the primary somatosensory cortex, the retinal projections and the spinal respiratory centres in these mice. The processes that have been found to be controlled by 5-HT levels in these in vivo models are axonal and dendritic remodelling, neuronal survival and neurogenesis. Knockouts and conditional knockouts for the genes that encode specific 5-HT receptor subtypes indicate that different 5-HT receptors control different developmental processes. For instance, 5-HT1B receptors are involved in axon arbour remodelling, 5-HT2B receptors in cell survival and 5-HT1A receptors in adult neurogenesis. Disturbance of these processes during the perinatal period has important consequences for adult behaviour. Investigations of genetic models with 5-HT target molecules provide interesting perspectives on developmental changes in the physiology of several psychiatric disorders.

Journal

Nature Reviews Neuroscience – Springer Journals

Published: Dec 1, 2003

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