LATE EFFECTS OF RETINOIC ACID ON NEURAL CREST AND ASPECTS OF RHOMBOMERE IDENTITY

We exposed st.10 chicks to retinoic acid (RA), both globally, and loca lly to individual rhombomeres, to look at its role in specification of various aspects of hindbrain derived morphology, Previous studies hav e looked at RA exposure at earlier stages, during axial specification. Stage 10 is the time of morphological segmentation of the hindbrain a nd is just prior to neural crest migration, Rhombomere 4 localised RA injections result in specific alterations of pathways some crest cells that normally migrate to sites of differentiation of neurogenic deriv atives, The r4 crest cells that give rise to mesenchymal derivatives a re unaffected, In addition, r4 gene expression is also partially alter ed by RA; within 6 hours of r4 exposure to RA, ectopic expression of K rox-20 is seen in r4 and Hoxb-1 expression is lost while Hoxa-2 expres sion continues normally, When we examined these RA-treated animals lat er in development, they showed an anterior displacement of the facial ganglion in addition to a mis-direction of the extensions of its dista l axons and a dramatic decrease in the number of contralateral vestibu loacoustic neurons normally seen in r4, Only this r4-specific neuronal type is affected in r4; the motor neuron projections seem normal in e xperimental animals, The specificity of this result, combined with the loss of Hoxb-1 expression in r4 and the work by Krumlauf and co-worke rs showing gain of contralateral neurons co-localised with ectopic Hox b-1 expression, indicates a role for Hoxb-1 and RA in the specificatio n of this cell type in normal development, These results suggest that RA, at st,10, is able to affect some aspects of segment identity while leaving others unchanged.