FIGURE 1.

Dynamics of signaling molecules and transcription factors regulating neural crest cell induction from blastula to neurula stage. Neural crest formation is viewed as a progressive inductive process initiating at blastula stage and continuing through gastrulation into neurula stage. This process is mediated by Wnt, FGF, and BMP signaling cues and transduced by transcription factors. Experimental data from works cited in this review were used to provide a temporal perspective of signaling and transcription factor modules involved during different phases of neural crest induction. Under the signaling module, dotted lines represent the potential role of these signaling molecules during blastula stages where their requirement is unknown. Based on expression patterns, BMP/Smad1/5/8 signaling is active at blastula stage (Faure, de Santa Barbara, Roberts, & Whitman, 2002) as well as Wnt and FGF/Erk1/2 signaling. During NC development, Wnt signaling is known to play a role during gastrula and neurula stages, FGF/Erk1/2 signaling during gastrula stage, and BMP/Smad1/5/8 signaling during neurula stage (denoted by solid lines), however, their role during pre-gastrula stage remains to be analyzed. FGF/Erk1/2 signaling is active during neurula stage; however, it is not suggested to be involved in NC development at this stage (grey line). BMP/Smad1/5/8 signaling is active during gastrula stage, but needs to be attenuated in cells specified towards NC fate, represented by the gap in the blue BMP signaling line. The transcription factor module provides a hierarchical view of the requirement of specific transcription factors during the different phases of neural crest induction. The transcription factors mentioned under blastula stage were identified from studies in a human neural crest model based on embryonic stem cells. The network of transcription factors involved in neural crest specification at blastula stage in animal models remains to be identified. NC = neural crest; NNE = nonneural ectoderm; NP = neural plate; pNC = prospective neural crest; pNP = prospective neural plate, PPE = preplacodal ectoderm). Schematics of gastrula and neurula chick embryos are adapted from Stuhlmiller & GarcííaCastro, 2012a