Pet-1 ETS gene plays a critical role in 5-HT neuron development and is required for normal anxiety-like and aggressive behavior

Neuron. 2003 Jan 23;37(2):233-47. doi: 10.1016/s0896-6273(02)01167-4.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


  • Biogenic Monoamines
  • Carrier Proteins
  • Fev protein, mouse
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, mouse
  • Transcription Factors
  • Serotonin