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

Chen Liu | Takashi Maejima | Steven C Wyler | Gemma Casadesus | Stefan Herlitze | Evan S Deneris
Nature neuroscience | 2010

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.

Pubmed ID: 20818386

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R01 MH062723-08
  • Agency: NIMH NIH HHS, United States
    Id: P50 MH078028-030001
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH062723-09
  • Agency: NIMH NIH HHS, United States
    Id: P50 MH078028-020001
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH062723-10
  • Agency: NIMH NIH HHS, United States
    Id: MH078028
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH062723-07
  • Agency: NIMH NIH HHS, United States
    Id: MH062723
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH062723
  • Agency: NIMH NIH HHS, United States
    Id: P50 MH078028
  • Agency: NIMH NIH HHS, United States
    Id: P50 MH078028-01A10001

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