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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.

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.

Pubmed ID: 12546819


  • Hendricks TJ
  • Fyodorov DV
  • Wegman LJ
  • Lelutiu NB
  • Pehek EA
  • Yamamoto B
  • Silver J
  • Weeber EJ
  • Sweatt JD
  • Deneris ES



Publication Data

January 23, 2003

Associated Grants

  • Agency: NIMH NIH HHS, Id: MH58926
  • Agency: NIMH NIH HHS, Id: MH62723
  • Agency: NINDS NIH HHS, Id: NS29123

Mesh Terms

  • Aggression
  • Alleles
  • Animals
  • Anxiety
  • Behavior, Animal
  • Biogenic Monoamines
  • Carrier Proteins
  • Cell Differentiation
  • Chromatography, High Pressure Liquid
  • Immunohistochemistry
  • In Situ Hybridization
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Nervous System
  • Neurons
  • Postural Balance
  • Rhombencephalon
  • Serotonin
  • Serotonin Plasma Membrane Transport Proteins
  • Transcription Factors