THE INDUCTIVE PROPERTIES OF MESODERM SUGGEST THAT THE NEURAL CREST CELLS ARE SPECIFIED BY A BMP GRADIENT

We have analyzed the role of mesoderm in the induction of the neural c rest in Xenopus using expression of neural plate (Xsox-2) and neural c rest (Xslug and ADAM). Conjugation experiments using different kinds o f mesoderm together with embryonic dissection experiments suggest that the dorsolateral mesoderm is capable of specifically inducing neural crest cells. Neural crest markers can be induced in competent ectoderm at varying distances from the inducing mesoderm, with dorsal tissue i nducing neural crest at a distance while dorsolateral tissue only indu ces neural crest directly in adjacent ectoderm. The results suggest th at dorsal mesoderm has a high level of inducer and dorsolateral mesode rm has a lower level, consistent with a inductive gradient. We explore d the possible role of BMP and noggin in the generation of such a hypo thetical gradient and found that: (1) progressively higher levels of B MP activity are sufficient for the specification of neural plate, neur al crest, and nonneural cells, respectively; (2) progressively higher levels of noggin are able to induce neural crest at greater distances from the source of inducer; and (3) modification of the levels of BMP activity causes induction of the neural crest in absence of neural pla te, suggesting independent induction of these two tissues. We propose a model in which a gradient of BMP activity is established in the ecto derm by interaction between BMP in the ectoderm and BMP inhibitors in the mesoderm. Neural crest is induced when a threshold level of BMP is attained in the ectoderm. The dorsolateral mesoderm produces either B MP inhibitors or a specific neural crest inducer, with low BMP activit y inducing neural plate while high BMP activity induces epidermis. (C) 1998 Academic Press.