Abstract
The central serotonin (5-HT) neurotransmitter system is an important modulator of diverse physiological processes and behaviors; however, the transcriptional mechanisms controlling its development are largely unknown. The Pet-1 ETS factor is a precise marker of developing and adult 5-HT neurons and is expressed shortly before 5-HT appears in the hindbrain. Here we show that in mice lacking Pet-1, the majority of 5-HT neurons fail to differentiate. Remaining ones show deficient expression of genes required for 5-HT synthesis, uptake, and storage. Significantly, defective development of the 5-HT system is followed by heightened anxiety-like and aggressive behavior in adults. These findings indicate that Pet-1 is a critical determinant of 5-HT neuron identity and implicate a Pet-1-dependent program in serotonergic modulation of behavior.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aggression / physiology*
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Alleles
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Animals
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Anxiety / genetics*
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Behavior, Animal / physiology
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Biogenic Monoamines / biosynthesis
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Carrier Proteins / biosynthesis
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Carrier Proteins / genetics
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Cell Differentiation / physiology
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Chromatography, High Pressure Liquid
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Immunohistochemistry
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In Situ Hybridization
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Membrane Transport Proteins*
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Mice
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Mice, Knockout
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Nerve Tissue Proteins*
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Nervous System / embryology
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Neurons / physiology*
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Postural Balance / physiology
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Rhombencephalon / physiology
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Serotonin / biosynthesis
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Serotonin / metabolism
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Serotonin / physiology*
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Serotonin Plasma Membrane Transport Proteins
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Transcription Factors / genetics*
Substances
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Biogenic Monoamines
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Carrier Proteins
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Fev protein, mouse
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Serotonin Plasma Membrane Transport Proteins
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Slc6a4 protein, mouse
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Transcription Factors
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Serotonin