Conclusions
During vertebrate evolution, motor neurons have undergone sequential changes in their organization in the spinal cord in accordance with the emergence of their peripheral targets (Fig. 6). In tetrapods, the forelimbs and hindlimbs are formed at the level of Hox6 and Hox10 expression, respectively, and the LMCs are segregated at the same levels in the spinal cord. The appearance of the LMCs seems to be linked to the emergence of paired limbs, and the Hox accessory factor FoxP1 may have played a critical role in the evolution of the LMC (Dasen et al., 2008). In the lineage of actinopterygian fishes, a Hox-dependent LMC has not been acquired, and there is no substantial evidence that specification of the appendicular motor neurons depends on the expression patterns of Hox genes in the spinal cord. It has been shown that primitive pectoral innervation originated from both the hindbrain and the spinal cord. Although caudal displacement of pectoral motor neurons during evolution can perhaps be explained by the positional shift of Hox expression in the spinal cord, future research should address whether pectoral motor neurons are specified by Hox expression in actinopterygians. Furthermore, the Hox-dependent mechanism of appendicular innervation has not been established with regard to pelvic fin innervation. It will be important to validate how and when the Hox-dependent appendicular innervation system was established during vertebrate evolution.