Zinc finger protein too few controls the development of monoaminergic neurons

Nat Neurosci. 2003 Jan;6(1):28-33. doi: 10.1038/nn979.

Abstract

The mechanism controlling the development of dopaminergic (DA) and serotonergic (5HT) neurons in vertebrates is not well understood. Here we characterized a zebrafish mutant--too few (tof)--that develops hindbrain 5HT and noradrenergic neurons, but does not develop hypothalamic DA and 5HT neurons. tof encodes a forebrain-specific zinc finger transcription repressor that is homologous to the mammalian Fezl (forebrain embryonic zinc finger-like protein). Mosaic and co-staining analyses showed that fezl was not expressed in DA or 5HT neurons and instead controlled development of these neurons non-cell-autonomously. Both the eh1-related repressor motif and the second zinc finger domain were necessary for tof function. Our results indicate that tof/fezl is a key component in regulating the development of monoaminergic neurons in the vertebrate brain.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Apoptosis / genetics
  • Biogenic Monoamines / metabolism*
  • Brain / cytology
  • Brain / embryology*
  • Brain / metabolism
  • Brain Tissue Transplantation
  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification*
  • Cell Differentiation / genetics*
  • Chromosome Mapping
  • Dopamine / metabolism
  • Embryo, Nonmammalian
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Male
  • Neurons / cytology
  • Neurons / metabolism*
  • Peptaibols
  • Peptides*
  • Repressor Proteins / genetics
  • Repressor Proteins / isolation & purification
  • Serotonin / metabolism
  • Signal Transduction / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Zebrafish
  • Zebrafish Proteins*
  • Zinc Fingers / genetics

Substances

  • Anti-Bacterial Agents
  • Biogenic Monoamines
  • Carrier Proteins
  • Peptaibols
  • Peptides
  • Repressor Proteins
  • Zebrafish Proteins
  • efrapeptin C
  • fezf2 protein, zebrafish
  • Serotonin
  • Dopamine