Fig. 8. A molecular model for neural crest induction. (A) At the early gastrula stage, Xiro1 induces the expression of Delta1 (and possibly Serrate) in a region that includes the neural crest territory. Later, Snail represses the expression of Delta1 in the prospective neural crest region, leaving a ring of cells expressing Delta1 at the border of the neural crest. (B) At the end of gastrulation, Xiro1 continues upregulating Delta1 at the border of the neural crest, and Delta1 interacts with Notch to induce the expression of Hairy2A in the neural folds. (C) Later on, Hairy2A acts as a repressor of Bmp4, ensuring that the levels of Bmp4 required to specify Xmsx1 expression and the formation of the neural folds are established. (D) Msx1, induced in the neural folds by the threshold levels of BMP activity, in combination with other signals, such as WNTs, FGFs and retinoic acid (RA), induces the formation of the neural crest at the border of the neural plate.