Saldivar J R, Sechrist J W, Krull C E, Ruffins S, Bronner-Fraser M
Division of Biology 139-74, California Institute of Technology, Pasadena 91125, USA.
Development. 1997 Jul;124(14):2729-39. doi: 10.1242/dev.124.14.2729.
Our previous studies have shown that hindbrain neural tube cells can regulate to form neural crest cells for a limited time after neural fold removal (Scherson, T., Serbedzija, G., Fraser, S. E. and Bronner-Fraser, M. (1993). Development 188, 1049-1061; Sechrist, J., Nieto, M. A., Zamanian, R. T. and Bronner-Fraser, M. (1995). Development 121, 4103-4115). In the present study, we ablated the dorsal hindbrain at later stages to examine possible alterations in migratory behavior and/or gene expression in neural crest populations rostral and caudal to the operated region. The results were compared with those obtained by misdirecting neural crest cells via rhombomere rotation. Following surgical ablation of dorsal r5 and r6 prior to the 10 somite stage, r4 neural crest cells migrate along normal pathways toward the second branchial arch. Similarly, r7 neural crest cells migrate primarily to the fourth branchial arch. When analogous ablations are performed at the 10-12 somite stage, however, a marked increase in the numbers of DiI/Hoxa-3-positive cells from r7 are observed within the third branchial arch. In addition, some DiI-labeled r4 cells migrate into the depleted hindbrain region and the third branchial arch. During their migration, a subset of these r4 cells up-regulate Hoxa-3, a transcript they do not normally express. Krox20 transcript levels were augmented after ablation in a population of neural crest cells migrating from r4, caudal r3 and rostral r3. Long-term survivors of bilateral ablations possess normal neural crest-derived cartilage of the hyoid complex, suggesting that misrouted r4 and r7 cells contribute to cranial derivatives appropriate for their new location. In contrast, misdirecting of the neural crest by rostrocaudal rotation of r4 through r6 results in a reduction of Hoxa-3 expression in the third branchial arch and corresponding deficits in third arch-derived structures of the hyoid apparatus. These results demonstrate that neural crest/tube progenitors in the hindbrain can compensate by altering migratory trajectories and patterns of gene expression when the adjacent neural crest is removed, but fail to compensate appropriately when the existing neural crest is misrouted by neural tube rotation.
我们之前的研究表明，在去除神经褶后的有限时间内，后脑神经管细胞可以调节形成神经嵴细胞（Scherson, T., Serbedzija, G., Fraser, S. E. 和 Bronner-Fraser, M. (1993). Development 188, 1049 - 1061; Sechrist, J., Nieto, M. A., Zamanian, R. T. 和 Bronner-Fraser, M. (1995). Development 121, 4103 - 4115）。在本研究中，我们在后期阶段切除背侧后脑，以检查手术区域头侧和尾侧神经嵴群体迁移行为和/或基因表达的可能变化。将结果与通过菱脑节旋转误导神经嵴细胞所获得的结果进行比较。在10体节阶段之前手术切除背侧r5和r6后，r4神经嵴细胞沿正常途径向第二鳃弓迁移。同样，r7神经嵴细胞主要迁移至第四鳃弓。然而，当在10 - 12体节阶段进行类似切除时，在第三鳃弓内观察到来自r7的DiI/Hoxa - 3阳性细胞数量显著增加。此外，一些DiI标记的r4细胞迁移到耗尽的后脑区域和第三鳃弓。在迁移过程中，这些r4细胞的一个亚群上调Hoxa - 3，这是一种它们通常不表达的转录本。在从r4、尾侧r3和头侧r3迁移的神经嵴细胞群体中，切除后Krox20转录水平增加。双侧切除的长期存活者具有舌骨复合体正常的神经嵴衍生软骨，这表明迷路的r4和r7细胞对适合其新位置的颅部衍生物有贡献。相比之下，通过r4至r6的头尾旋转误导神经嵴会导致第三鳃弓中Hoxa - 3表达减少以及舌骨装置第三弓衍生结构出现相应缺陷。这些结果表明，当相邻神经嵴被去除时，后脑的神经嵴/神经管祖细胞可以通过改变迁移轨迹和基因表达模式进行补偿，但当现有的神经嵴因神经管旋转而迷路时，它们无法进行适当的补偿。
