Fig. 8. A model of consecutive step of the neural crest specification. (A) A proposed model of sequential steps of neural crest specification. (Phase I) During gastrulation, midline BMP antagonists inhibit BMP4 expression and specify the neural plate (orange). After this, X-TSK expression is repressed in the presumptive neural plate (yellow), while it is maintained in the lateral ectoderm by BMP4 signaling. (Phase II) After stage 12.5, X-TSK expression is upregulated in the presumptive neural crest region, which has intermediate levels of BMP signaling. (siRNA) In X-TSK depleted embryo, BMP signaling levels (green) are increased in the TSK expressing-region. Under these conditions, epidermal fates are expanded up to the neural plate margin (blue), while the neural crest region (yellow) is repressed. (B) Molecular network of neural crest specification. X-TSK inhibits BMP4 (red asterisk) and modulates Notch signaling via direct binding to X-delta-1 (purple asterisk). Notch signaling can regulate the expression of BMP4, and BMP and Notch signaling interact to control the expression of Hairy2A and Msx1. Timing of Notch activation alters its effect on BMP4 expression (see Glavic et al., 2004) (black asterisk). Finally, caudalizing signals such as XWnt-8 converge on this network downstream of Msx1 to control the activation of Pax3 expression and neural crest cell specification within the Msx1-expressing region. The interactions indicated by `1' and `2' have been reported previously (Glavic et al., 2004; Monsoro-Burq et al., 2005).