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Several genes encoding transcription factors are expressed in the neural crest at different times during development. Functional studies suggest that they are involved in neural crest specification, migration or differentiation. However, very little is known about the hierarchical relationship between them or about their specific roles during neural crest specification.
Order of transcription factors
Based on our model of induction and posteriorization we expect that the first genes required for crest induction should be expressed along the entire border of the neural plate. In contrast, genes involved in later processes should be restricted to the prospective neural crest region rather than being expressed in the most anterior neural folds.
Thus, based on their spatial and temporal expression patterns, we have grouped 9 of these transcription factors in the following order:
- Msx1, Hairy2A
- Snail, Zic5
- Slug, FoxD3, Twist
- Sox9, Sox10.
However, these criteria are not sufficient, as they are based on gene expression and not on the detection of the protein. Indeed, an undetectable amount of protein of one of these factors could be enough to trigger strong expression of another factor whose mRNA is easily detectable at an apparently earlier stage. Functional studies are therefore necessary.
Our tools
We have generated inducible forms of wild type and dominant negative proteins for many of these factors. We are analyzing the relationship between several of these transcription factors and establishing which of these genes are direct regulators of the expression of the other genes.
In addition, we are analyzing the role of all these transcription factors in the different steps of Neural Crest development.