Zebrafish foxd3 is selectively required for neural crest specification, migration and survival

Stewart, R.A., Arduini, B.L., Berghmans, S., George, R.E., Kanki, J.P., Henion, P.D., and Look, A.T.
Developmental Biology   292(1): 174-188 (Journal)
Registered Authors
Arduini, Brigitte, George, Rani, Henion, Paul, Kanki, John, Look, A. Thomas, Stewart, Rodney A.
Neural crest, foxd3, Sympathetic, sox10, snai1b, Survival, Migration, Specification, Zebrafish
MeSH Terms
  • Animals
  • Cell Lineage/genetics
  • Cell Lineage/physiology
  • Cell Movement/genetics
  • Cell Movement/physiology*
  • Cell Survival/genetics
  • Cell Survival/physiology
  • Female
  • Forkhead Transcription Factors/deficiency
  • Forkhead Transcription Factors/genetics
  • Forkhead Transcription Factors/physiology*
  • Neural Crest/cytology*
  • Neural Crest/embryology*
  • Neural Crest/physiology
  • Sympathetic Nervous System/cytology
  • Sympathetic Nervous System/physiology
  • Transcription Factors/biosynthesis
  • Transcription Factors/physiology
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/physiology
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
16499899 Full text @ Dev. Biol.
The vertebrate neural crest is a pluripotent cell population that generates a large variety of cell types, including peripheral neurons, cartilage and pigment cells. Mechanisms that control the patterning of the neural crest toward specific cell fates remain only partially understood. Zebrafish homozygous for the sympathetic mutation 1 (sym1) have defects in a subset of neural crest derivatives, such as peripheral neurons, glia and cartilage, but retain normal numbers of melanocytes. The sym1 mutation is a nucleotide deletion that disrupts the forkhead DNA-binding domain of the foxd3 gene, which encodes a conserved winged-helix transcription factor. We show that sym1 mutants have normal numbers of premigratory neural crest cells, but these cells express reduced levels of snai1b and sox10, implicating foxd3 as an essential regulator of these transcription factors in the premigratory neural crest. The onset of neural crest migration is also delayed in sym1 mutants, and there is a reduction in the number of migratory trunk neural crest cells, particularly along the medial migration pathway. TUNEL analysis revealed aberrant apoptosis localized to the hindbrain neural crest at the 15-somite stage, indicating a critical role for foxd3 in the survival of a subpopulation of neural crest cells. These results show that foxd3 selectively specifies premigratory neural crest cells for a neuronal, glial or cartilage fate, by inducing the expression of lineage-associated transcription factors in these cells and regulating their subsequent migration.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes