Yamamoto M, Gotoh Y, Tamura K, Tanaka M, Kawakami A, Ide H, Kuroiwa A
Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan.
Development. 1998 Apr;125(7):1325-35. doi: 10.1242/dev.125.7.1325.
The limb muscle precursor cells migrate from the somites and congregate into the dorsal and ventral muscle masses in the limb bud. Complex muscle patterns are formed by successive splitting of the muscle masses and subsequent growth and differentiation in a region-specific manner. Hox genes, known as key regulator genes of cartilage pattern formation in the limb bud, were found to be expressed in the limb muscle precursor cells. We found that HOXA-11 protein was expressed in the premyoblasts in the limb bud, but not in the somitic cells or migrating premyogenic cells in the trunk at stage 18. By stage 24, HOXA-11 expression began to decrease from the posterior halves of the muscle masses. HOXA-13 was expressed strongly in the myoblasts of the posterior part in the dorsal/ventral muscle masses and weakly in a few myoblasts of the anterior part of the dorsal muscle mass. Transplantation of the lateral plate of the presumptive wing bud to the flank induced migration of premyoblasts from somites to the graft. Under these conditions, HOXA-11 expression was induced in the migrating premyoblasts in the ectopic limb buds. Application of retinoic acid at the anterior margin of the limb bud causes duplication of the autopodal cartilage and transformation of the radius to the ulna, and at the same time induces duplication of the muscle pattern along the anteroposterior axis. Under these conditions, HOXA-13 was also induced in the anterior region of the ventral muscles in the zeugopod. These results suggest that Hoxa-11 and Hoxa-13 expression in the migrating premyoblasts is under the control of the limb mesenchyme and the polarizing signal(s). In addition, these results indicate that these Hox genes are involved in muscle patterning in the limb buds.
肢体肌肉前体细胞从体节迁移至肢体芽中的背侧和腹侧肌肉团块。复杂的肌肉模式是由肌肉团块的连续分裂以及随后以区域特异性方式的生长和分化形成的。Hox基因是肢体芽中软骨模式形成的关键调节基因，被发现可在肢体肌肉前体细胞中表达。我们发现HOXA - 11蛋白在肢体芽中的成肌前体细胞中表达，但在第18阶段时，在体节细胞或躯干中迁移的成肌前体细胞中不表达。到第24阶段，HOXA - 11的表达开始从肌肉团块的后半部分下降。HOXA - 13在背侧/腹侧肌肉团块后部的成肌细胞中强烈表达，在背侧肌肉团块前部的少数成肌细胞中弱表达。将假定翼芽的侧板移植到侧翼会诱导成肌前体细胞从体节迁移至移植部位。在这些条件下，异位肢体芽中迁移的成肌前体细胞中会诱导HOXA - 11的表达。在肢体芽前缘施加视黄酸会导致自手软骨重复以及桡骨向尺骨的转化，同时还会沿前后轴诱导肌肉模式的重复。在这些条件下，zeugopod腹侧肌肉的前部区域也会诱导HOXA - 13的表达。这些结果表明，迁移的成肌前体细胞中Hoxa - 11和Hoxa - 13的表达受肢体间充质和极化信号的控制。此外，这些结果表明这些Hox基因参与了肢体芽中的肌肉模式形成。
