Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior.
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.
Hendricks
Timothy J
TJ
Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Fyodorov
Dmitry V
DV
Wegman
Lauren J
LJ
Lelutiu
Nadia B
NB
Pehek
Elizabeth A
EA
Yamamoto
Bryan
B
Silver
Jerry
J
Weeber
Edwin J
EJ
Sweatt
J David
JD
Deneris
Evan S
ES
D000374:Aggression / Q000502:physiology*; D000483:Alleles; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology; D015306:Biogenic Monoamines / Q000096:biosynthesis; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D009420:Nervous System / Q000196:embryology; D009474:Neurons / Q000502:physiology*; D004856:Postural Balance / Q000502:physiology; D012249:Rhombencephalon / Q000502:physiology; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins; D014157:Transcription Factors / Q000235:genetics*
D015306:Biogenic Monoamines; D002352:Carrier Proteins; C484684:Fev protein, mouse; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D014157:Transcription Factors; D012701:Serotonin