Key-notes on Neural Induction

The default model is based on the idea that inhibiting BMP signaling is both necessary and sufficient to induce neural tissue to form, and that the organizer secretes BMP inhibitors to assure that BMP signaling is kept low on the dorsal side where neural tissue form. Thus, differential BMP signaling in Xenopus and zebrafish fulfills the expectation of an instructive mechanism for determining why neural tissue forms in one place in the embryo but not another. The default model, however, leaves open the possibility that other factors are involved in neural induction, including those operating in a more permissive fashion to alter the competence of the ectoderm. This is critical in birds and mammals where the spatial and temporal expression pattern of the BMPs and their inhibitors does not fit with the neural default model of induction. The best evidence for a factor is for fibroblast growth factor (FGF) and IGF, a ligand that binds to its receptors and signals via the MAPK cascade. FGF signaling is prominent in the early embryos during the process of mesodermal induction, and has also been shown to play an important role in posterior neural patterning. Significantly, FGF signaling has also been shown to inhibit BMP signaling in the early embryo by several mechanisms, thus potentially influencing the response of tissue to the activity of the BMP inhibitors produced by the organizer during neural induction. FGF signaling can promote phosphorylation of the linker domain and degradation of Smad1, thus reducing the efficacy of BMP signaling. FGF signaling can also inhibit BMP activity indirectly, by inducing the expression of a protein called SIP1, a zinc-finger, homeodomain protein, that binds to and represses the transcriptional activity of the Smad protein. For much of the neural plate, the role of FGF signaling is likely to be minor, since neural induction by the BMP inhibitors occurs readily in Xenopus in the absence of FGF signaling. Nonetheless, for the parts of the posterior neural plate located far from the organizer on the blastula fate map, prior FGF signaling may be required as a priming mechanism to suppress BMP signaling, so that the BMP antagonists can consolidate and maintain a commitment to a neural fate at later stages.