Developmental Mechanism of Limb Field Specification along the Anterior–Posterior Axis during Vertebrate Evolution

In gnathostomes, limb buds arise from the lateral plate mesoderm at discrete positions along the body axis. Specification of these limb-forming fields can be subdivided into several steps. The lateral plate mesoderm is regionalized into the anterior lateral plate mesoderm (ALPM; cardiac mesoderm) and the posterior lateral plate mesoderm (PLPM). Subsequently, Hox genes appear in a nested fashion in the PLPM and provide positional information along the body axis. The lateral plate mesoderm then splits into the somatic and splanchnic layers. In the somatic layer of the PLPM, the expression of limb initiation genes appears in the limb-forming region, leading to limb bud initiation. Furthermore, past and current work in limbless amphioxus and lampreys suggests that evolutionary changes in developmental programs occurred during the acquisition of paired fins during vertebrate evolution. This review presents these recent advances and discusses the mechanisms of limb field specification during development and evolution, with a focus on the role of Hox genes in this process.