The neural crest is a powerful regulator of pre-otic brain development.

The role of the neural crest (NC) in the construction of the vertebrate head was demonstrated when cell tracing techniques became available to follow the cells exiting from the cephalic neural folds in embryos of various vertebrate species. Experiments carried out in the avian embryo, using the quail/chick chimera system, were critical in showing that the entire facial skeleton and most of the skull (except for he occipital region) were derived from the NC domain of the posterior diencephalon, mesencephalon and rhombomeres 1 and 2 (r1, r2). This region of the NC was designated FSNC (for Facial Skeletogenic NC). One characteristic of this part of the head including the neural anlage is that it remains free of expression of the homeotic genes of the Hox-clusters. In an attempt to see whether this rostral Hox-negative domain of the NC has a specific role in the development of the skeleton, we have surgically removed it in chick embryos at 5-6 somite stages (5-6 ss). The operated embryos showed a complete absence of facial and skull cartilages and bones showing that the Hox expressing domain of the NC caudally located to the excision did not regenerate to replace the anterior NC. In addition to the deficit in skeletal structures, the operated embryos exhibited severe brain defects resulting in anencephaly. Experiments described here have shown that the neural crest cells regulate the amount of Fgf8 produced by the two brain organizers, the Anterior Neural Ridge (ANR) and the isthmus. This regulation is exerted via the secretion of anti-BMP signaling molecules (e.g. Gremlin and Noggin), which decrease BMP production hence enhancing the amount of Fgf8 synthesized in the ANR (also called "Prosencephalic organizer") and the isthmus. In addition to its role in building up the face and skull, the NC is therefore an important signaling center for brain development.