Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior

Timothy J. Hendricks; Dmitry V. Fyodorov; Lauren J. Wegman; Nadia B. Lelutiu; Elizabeth A. Pehek; Bryan Yamamoto; Jerry Silver; Edwin J. Weeber; J. David Sweatt; Evan S. Deneris

doi:10.1016/S0896-6273(02)01167-4

Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior

Timothy J. Hendricks, Dmitry V. Fyodorov, Lauren J. Wegman, Nadia B. Lelutiu, Elizabeth A. Pehek, Bryan Yamamoto, Jerry Silver, Edwin J. Weeber, J. David Sweatt, Evan S. Deneris

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405 Scopus citations

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.

Original language	English (US)
Pages (from-to)	233-247
Number of pages	15
Journal	Neuron
Volume	37
Issue number	2
DOIs	https://doi.org/10.1016/S0896-6273(02)01167-4
State	Published - Jan 23 2003
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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10.1016/S0896-6273(02)01167-4

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title = "Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior",

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.",

author = "Hendricks, {Timothy J.} and Fyodorov, {Dmitry V.} and Wegman, {Lauren J.} and Lelutiu, {Nadia B.} and Pehek, {Elizabeth A.} and Bryan Yamamoto and Jerry Silver and Weeber, {Edwin J.} and Sweatt, {J. David} and Deneris, {Evan S.}",

note = "Funding Information: We thank Robert Miller for comments on the final draft and Ben Strowbridge, Byran Roth, and Stephen O'Gorman for comments on an earlier draft. A special thanks to Andy Russo for suggesting the University of Iowa Gene Targeting Core Facility and overseeing the ES stem cell and chimera production contract. We thank Howard Rind and Scott Whittemore for the rat TPH cDNA. This research was supported by MH58926, MH62723, and NS29123 to E.S.D. and by an NIH predoctoral traineeship to T.J.H.",

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doi = "10.1016/S0896-6273(02)01167-4",

language = "English (US)",

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T1 - Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior

AU - Hendricks, Timothy J.

AU - Fyodorov, Dmitry V.

AU - Wegman, Lauren J.

AU - Lelutiu, Nadia B.

AU - Pehek, Elizabeth A.

AU - Yamamoto, Bryan

AU - Silver, Jerry

AU - Weeber, Edwin J.

AU - Sweatt, J. David

AU - Deneris, Evan S.

N1 - Funding Information: We thank Robert Miller for comments on the final draft and Ben Strowbridge, Byran Roth, and Stephen O'Gorman for comments on an earlier draft. A special thanks to Andy Russo for suggesting the University of Iowa Gene Targeting Core Facility and overseeing the ES stem cell and chimera production contract. We thank Howard Rind and Scott Whittemore for the rat TPH cDNA. This research was supported by MH58926, MH62723, and NS29123 to E.S.D. and by an NIH predoctoral traineeship to T.J.H.

PY - 2003/1/23

Y1 - 2003/1/23

N2 - 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.

AB - 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.

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Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior

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