EVEN-NUMBERED RHOMBOMERES CONTROL THE APOPTOTIC ELIMINATION OF NEURALCREST CELLS FROM ODD-NUMBERED RHOMBOMERES IN THE CHICK HINDBRAIN

Neural crest cells originate at three discontinuous levels along the r ostrocaudal axis of the chick rhombencephalon, centred on rhombomeres 1 and 2, 4 and 6, respectively. These are separated by the odd-numbere d rhombomeres r3 and r5 which are depleted of migratory neural crest c ells. Here we show elevated levels of apoptosis in the dorsal midline of r3 and r5, immediately following the formation of these rhombomeres at the developmental stage (10-12) when neural crest cells would be e xpected to emerge at these neuraxial levels. These regions are also ma rked by their expression of members of the msx family of homeobox gene s with msx-2 expression preceding apoptosis in a precisely co-localise d pattern. In vitro and in ovo experiments have revealed that r3 and r 5 are depleted of neural crest cells by an interaction within the neur al epithelium: if isolated or distanced from their normal juxtapositio n with even-numbered rhombomeres, both r3 and r5 produce migrating neu ral crest cells. When r3 or r5 are unconstrained in this way, allowing production of crest, msx-2 expression is concomitantly down regulated . This suggests a correlation between msx-2 and the programming of apo ptosis in this system. The hindbrain neural crest is thus produced in discrete streams by mechanisms intrinsic to the neural epithelium. The crest cells that enter the underlying branchial region are organised into streams before they encounter the mesodermal environment lateral to the neural tube. This contrasts sharply with the situation in the t runk where neural crest production is uninterrupted along the neuraxis and the segmental accumulation of neurogenic crest cells is subsequen tly founded on an alternation of permissive and non-permissive qualiti es of the local mesodermal environment.