Pet-1 is required across different stages of life to regulate serotonergic function.

Liu C, Maejima T, Wyler SC, Casadesus G, Herlitze S, Deneris ES
Nat Neurosci. 2010 13 (10): 1190-8

PMID: 20818386 · PMCID: PMC2947586 · DOI:10.1038/nn.2623

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.

MeSH Terms (34)

8-Hydroxy-2-(di-n-propylamino)tetralin Age Factors Analysis of Variance Animals Animals, Newborn Cell Differentiation Chromatin Immunoprecipitation Estrogen Antagonists Excitatory Amino Acid Antagonists Extracellular Matrix Proteins Gene Expression Regulation, Developmental In Vitro Techniques Luminescent Proteins Male Maze Learning Mice Mice, Inbred C57BL Mice, Transgenic Motor Activity Neurons Patch-Clamp Techniques Protein-Lysine 6-Oxidase Raphe Nuclei Receptor, Serotonin, 5-HT1A Receptor, Serotonin, 5-HT1B RNA, Messenger Serotonin Serotonin Plasma Membrane Transport Proteins Serotonin Receptor Agonists Somatosensory Cortex Tamoxifen Transcription Factors Tryptophan Hydroxylase Xanthenes

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