NEURAL CREST EMIGRATION FROM THE NEURAL-TUBE DEPENDS ON REGULATED CADHERIN EXPRESSION

During the emergence of neural crest cells from the neural tube, the e xpression of cadherins dynamically changes. In the chicken embryo, the early neural tube expresses two cadherins, N-cadherin and cadherin-6B (cad6B), in the dorsal-most region where neural crest cells are gener ated. The expression of these two cadherins is, however, downregulated in the neural crest cells migrating from the neural tube; they instea d begin expressing cadherin-7 (cad7). As an attempt to investigate the role of these changes in cadherin expression, we overexpressed variou s cadherin constructs, including N-cadherin, cad7, and a dominant nega tive N-cadherin (cN390 Delta), in neural crest-generating cells. This was achieved by injecting adenoviral expression vectors encoding these molecules into the lumen of the closing neural tube of chicken embryo s at stage 14, In neural tubes injected with the viruses, efficient in fection was observed at the neural crest-forming area, resulting in th e ectopic cadherin expression also in migrating neural crest cells. No tably, the distribution of neural crest cells with the ectopic cadheri ns changed depending on which constructs were expressed. Many crest ce lls failed to escape from the neural tube when N-cadherin or cad7 over expressed. Moreover, none of the cells with these ectopic cadherins mi grated along the dorsolateral (melanocyte) pathway. When these samples were stained for Mitf, an early melanocyte marker, positive cells wer e found accumulated within the neural tube, suggesting that the failur e of their migration was not due to differentiation defects. In contra st to these phenomena, cells expressing non-functional cadherins exhib ited a normal migration pattern. Thus, the overexpression of a neuroep ithelial cadherin (N-cadherin) and a crest cadherin (cad7) resulted in the same blocking effect on neural crest segregation from neuroepithe lial cells, especially for melanocyte precursors. These findings sugge st that the regulation of cadherin expression or its activity at the n eural crest-forming area plays a critical role in neural crest emigrat ion from the neural tube.