Pet-1 is required across different stages of life to regulate serotonergic function.
Transcriptional cascades are required for the specification of serotonin (5-HT) neurons and behaviors modulated by 5-HT. Several cascade factors are expressed throughout the lifespan, which suggests that their control of behavior might not be temporally restricted to programming normal numbers of 5-HT neurons. We used new mouse conditional targeting approaches to investigate the ongoing requirements for Pet-1 (also called Fev), a cascade factor that is required for the initiation of 5-HT synthesis, but whose expression persists into adulthood. We found that Pet-1 was required after the generation of 5-HT neurons for multiple steps in 5-HT neuron maturation, including axonal innervation of the somatosensory cortex, expression of appropriate firing properties, and the expression of the Htr1a and Htr1b autoreceptors. Pet-1 was still required in adult 5-HT neurons to preserve normal anxiety-related behaviors through direct autoregulated control of serotonergic gene expression. These findings indicate that Pet-1 is required across the lifespan of the mouse and that behavioral pathogenesis can result from both developmental and adult-onset alterations in serotonergic transcription.
Liu
Chen
C
Case Western Reserve University, School of Medicine, Department of Neurosciences, Cleveland, Ohio, USA.
Maejima
Takashi
T
Wyler
Steven C
SC
Casadesus
Gemma
G
Herlitze
Stefan
S
Deneris
Evan S
ES
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation / Q000379:methods; D004965:Estrogen Antagonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000166:cytology / Q000196:embryology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D012701:Serotonin / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013003:Somatosensory Cortex / Q000166:cytology / Q000196:embryology; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014966:Xanthenes / Q000378:metabolism
D004965:Estrogen Antagonists; D018691:Excitatory Amino Acid Antagonists; D016326:Extracellular Matrix Proteins; C484684:Fev protein, mouse; D008164:Luminescent Proteins; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; C493231:Slc6a4 protein, mouse; D014157:Transcription Factors; D014966:Xanthenes; D013629:Tamoxifen; D044282:Receptor, Serotonin, 5-HT1A; C077112:Lox protein, mouse; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C034657:Texas red; D014365:Tryptophan Hydroxylase; D008249:Protein-Lysine 6-Oxidase
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