Neural Crest Migration

Following their induction in the dorsolateral neural tube, neural crest cells undergo an epithelial to mesenchymal transition (EMT), become motile and start to migrate. However not much is known about the molecular basis of any of these process.

Most of the studies on crest migration have been focused on the changes in cell-cell and cell-matrix interactions and the role of extracellular matrix and adhesion molecules, but very few have explored the intracellular machinery regulating cell migration.

Important molecular factors during cell migration

A number of intracellular factors have been identified as playing a role in the migration of other cells in vitro. Among them, the Rho family of small GTPases, RhoA, Rac1, and Cdc42 has been studied most intensively.

Each of the three members has a distinct function in actin cytoskeletal organization and responses:

• Rho has been shown to regulate the formation of actin stress fibers and focal adhesion in fibroblasts.
• Rac1 induces membrane ruffling and lamellipodia formation
• Cdc42 mediates the formation of filopodia and actin microspikes.

 

Xenopus and zebrafish as a model system for Neural Crest cell migration

Because of the remarkable migratory behaviour, the ease with which it is possible to work with this cell population and the amount of information available, we will analyse the cellular changes of crest cells during their migration and explore the intracellular machinery regulating this process in Xenopus and zebrafish embryos.

Our aim is to study neural crest cell migration in vivo and in vitro, under normal conditions as well as in the presence of dominant negative or mutant forms of some of the molecules described above.

We have recently shown that the non-canonical Wnt signaling is required for Neural Crest migration; but we do not understand how this signaling controls the directional migration of the neural crest cell in the embryo.

Our tools

We can study the migration of the Neural Crest in zebrafish by using transgenic lines that express fluorescent proteins specifically in the Neural Crest cells.

In Xenopus DiI labeling or grafts of fluorescent Neural Crest into control host can also be used to study Neural Crest migration in vivo.

Finally, dissection and in vitro culture of NC is a complementary approach to the in vivo experiments and allows to test some of the in vivo finding in a more controlled environment findings.

With all this tools we are also developing screens to identify new molecules involved in Neural Crest migration.