Figure 9.

A model for Draxin’s control of cranial neural crest EMT. (A) Under WT conditions, Draxin is expressed in premigratory cranial neural crest between stages HH9− and HH9. While Draxin is present (left), tight control of canonical Wnt activation and inhibition maintains a balance of Snail2 and Cad6B expression, and neural crest cells are retained within the neural tube. When Draxin is knocked down (right) before EMT, there is an increase in canonical Wnt signaling, which causes an increase in Snail2 and decrease in Cad6b; this induces premature delamination of neural crest from the neural tube with a subsequent reduction in neural crest cell numbers and migration. (B) Under WT conditions, Draxin is down-regulated when cranial neural crest becomes migratory at stage HH9+. When Draxin is absent at this stage (left), the loss of canonical Wnt inhibition induces Cad6B repression via Snail2, and neural crest cells delaminate from the neural tube and mesenchymalize to migrate away from the midline. When Draxin is overexpressed at HH9+ (right), increased inhibition of canonical Wnt up-regulates levels of Cad6B both within the neural tube, reducing neural crest delamination, and in the migratory neural crest; however, maintenance of Cad6B expression in migratory neural crest reduces their mesenchymalization and migratory ability. Yellow circles indicate neural crest cells; orange lines indicate Cad6B.