PMID:11262245

Citation	Kos, R, Reedy, MV, Johnson, RL and Erickson, CA (2001) The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos. Development 128:1467-79
Abstract	The winged-helix or forkhead class of transcription factors has been shown to play important roles in cell specification and lineage segregation. We have cloned the chicken homolog of FoxD3, a member of the winged-helix class of transcription factors, and analyzed its expression. Based on its expression in the dorsal neural tube and in all neural crest lineages except the late-emigrating melanoblasts, we predicted that FoxD3 might be important in the segregation of the neural crest lineage from the neural epithelium, and for repressing melanogenesis in early-migrating neural crest cells. Misexpression of FoxD3 by electroporation in the lateral neural epithelium early in neural crest development produced an expansion of HNK1 immunoreactivity throughout the neural epithelium, although these cells did not undergo an epithelial/mesenchymal transformation. To test whether FoxD3 represses melanogenesis in early migrating neural crest cells, we knocked down expression in cultured neural crest with antisense oligonucleotides and in vivo by treatment with morpholino antisense oligonucleotides. Both experimental approaches resulted in an expansion of the melanoblast lineage, probably at the expense of neuronal and glial lineages. Conversely, persistent expression of FoxD3 in late-migrating neural crest cells using RCAS viruses resulted in the failure of melanoblasts to develop. We suggest that FoxD3 plays two important roles in neural crest development. First, it is involved in the segregation of the neural crest lineage from the neuroepithelium. Second, it represses melanogenesis, thereby allowing other neural crest derivatives to differentiate during the early stages of neural crest patterning.
Links	PubMed
Keywords	Alpharetrovirus; Amino Acid Sequence; Animals; Cell Differentiation; Cell Lineage; Cell Movement/physiology; Chick Embryo; Cloning, Molecular; Coturnix; DNA-Binding Proteins/biosynthesis; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Epithelium; Forkhead Transcription Factors; Gene Expression; Gene Expression Regulation, Developmental; Genetic Vectors; Humans; Mesencephalon/embryology; Mice; Molecular Sequence Data; Neural Crest/cytology; Neural Crest/embryology; Neural Crest/physiology; Oligodeoxyribonucleotides, Antisense; Repressor Proteins/biosynthesis; Repressor Proteins/genetics; Repressor Proteins/physiology; Sequence Analysis, DNA; Transcription Factors/biosynthesis; Transcription Factors/genetics; Transcription Factors/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
CHICK:FOXD3		GO:0045635: negative regulation of melanocyte differentiation	ECO:0000315:		P		In figure 6 and table 1, there are results with three different Foxd3 antisense oligonucleotide treatments. When Foxd3 expression was reduced with this treatment, 38.5% of cells differentiated into melanocytes versus 18% of the control (statistically significant using Tukey analysis). This suggests that Foxd3 negatively regulated melanocyte differentiation.	complete
CHICK:FOXD3		GO:0001755: neural crest cell migration	ECO:0000270:		P		Figure 3 shows that if you have ectopically express Foxd3, you can get ecotopic expression of HNK-1 and Cad-7 in a way that suggests that they are migrating away from the neural tube, similar to the migration of neural crest cells. HNK-1 is normally only expressed in migrating neural crest cells, so its induction by Foxd3 suggests that Foxd3 induces migratory neural crest cells.	complete

References

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