Development of noradrenergic neurons in the zebrafish hindbrain requires BMP, FGF8, and the homeodomain protein soulless/Phox2a

Neuron. 1999 Nov;24(3):555-66. doi: 10.1016/s0896-6273(00)81112-5.


We report that the zebrafish mutation soulless, in which the development of locus coeruleus (LC) noradrenergic (NA) neurons failed to occur, disrupts the homeodomain protein Phox2a. Phox2a is not only necessary but also sufficient to induce Phox2b+ dopamine-beta-hydroxylase+ and tyrosine hydroxylase+ NA neurons in ectopic locations. Phox2a is first detected in LC progenitors in the dorsal anterior hindbrain, and its expression there is dependent on FGF8 from the mid/hindbrain boundary and on optimal concentrations of BMP signal from the epidermal ectoderm/future dorsal neural plate junction. These findings suggest that Phox2a coordinates the specification of LC in part through the induction of Phox2b and in response to cooperating signals that operate along the mediolateral and anteroposterior axes of the neural plate.

Publication types

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

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Bone Morphogenetic Proteins / physiology*
  • Dopamine beta-Hydroxylase / metabolism
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / physiology
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / physiology*
  • Homeodomain Proteins / physiology*
  • Locus Coeruleus / embryology
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • Neurons / metabolism
  • Neurons / physiology*
  • Norepinephrine / physiology*
  • Rhombencephalon / embryology*
  • Sequence Homology, Amino Acid
  • Stem Cells / metabolism
  • Transcription Factors / physiology*
  • Tyrosine 3-Monooxygenase / metabolism
  • Zebrafish / embryology
  • Zebrafish Proteins / physiology*


  • Bone Morphogenetic Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Phox2a protein, zebrafish
  • Transcription Factors
  • Zebrafish Proteins
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors
  • Tyrosine 3-Monooxygenase
  • Dopamine beta-Hydroxylase
  • Norepinephrine