THE SIGNALING MOLECULE BMP4 MEDIATES APOPTOSIS IN THE RHOMBENCEPHALICNEURAL CREST

THE pattern of skeletal structures and muscles in the branchial region of the head is profoundly influenced by the neural crest whose cells arise at discrete segmental levels of the chick hindbrain: specificall y, rhombomeres (r)1 + 2, r4 and r6, whereas r3 and r5 are crest-deplet ed(2). We have demonstrated that an interaction between even-numbered rhombomeres and r3/r5 effects this depletion of neural crest, resultin g in the sculpting of discrete migratory streams of neural crest(3). T his mechanism acts through increased expression of msx2 and the induct ion of apoptosis in dorsal cells of r3 and r5 (ref. 3) (Fig. 1A). Here we demonstrate that the signalling molecule Bmp4 is expressed in r3 a nd r5 and is dependent on the neighbouring rhombomeres. Addition of re combinant BMP4 protein to explant cultures of r3 or r5, which produce neural crest when isolated from their neighbouring rhombomeres, upregu lates msx2 and reinstates apoptosis in the neural crest population.