Restricting Bmp-4 mediated apoptosis in hindbrain neural crest.

The segregation of the rhombencephalic neural crest into three streams, destined for particular pharyngeal arches, is a prominent feature of the developing vertebrate head and is likely necessary for normal morphogenesis. At least in part, the segregation of the crest into these streams involves the focal depletion of neural crest from rhombomeres 3 and 5 through large-scale apoptosis, mediated by the induction of Bmp-4 expression in the crest primordia of these two rhombomeres. Previously we found that in contrast to rhombomeres 3 and 5, the intervening segment rhombomere 4 was not susceptible to Bmp-4-sponsored neural crest cell death. To analyse the reason for this difference, we have isolated clones for the necessary components of the Bmp-4 signal transduction apparatus. We find that the hindbrain neural crest generally is primed to respond to Bmp-4 and that in vitro, besides rhombomere 3 and 5, rhombomeres 2 and 6 are also sensitive to Bmp-4-sponsored death. As before, however, we find that rhombomere 4 will not respond to this factor. Our analysis of the Bmp-4 antagonists has uncovered a reason for this. Rhombomere 4 expresses elevated levels of the antagonist Noggin at its dorsal midline just as crest production from this segment commences and, as development proceeds, in the crest that migrates away from there. At these later stages, expression also becomes apparent in the migratory post-otic crest as it flows by the otic vesicle. An interesting feature of these domains of Noggin expression is that they lie between territories of Bmp-4 expression, suggesting that Noggin is acting to protect from Bmp-4-mediated cell death.