Recent advances in the study of limb development: the emergence and function of the apical ectodermal ridge.

Vertebrate extremities develop from limb buds, which emerge as paired protrusions in the lateral plate mesoderm. Forelimb buds are located anteriorly and hindlimb buds are positioned posteriorly. The morphogenesis of the limb requires coordinated actions of several organizing centers, among which the apical ectodermal ridge (AER) plays crucial roles in limb development. Recent studies have shown how the life of the AER (induction, maturation, maintenance and regression) is regulated. This regulation includes cell type- and process- specific roles of previously identified molecules, such as fibroblast growth factors (FGFs), Wnts and bone morphogenetic proteins (BMPs). The studies have also revealed several new players, such as Arid3b, R-Spondin 2 and Flrt3. These advances have enhanced the understanding of how the AER is regulated from its emergence to its regression. Progress has also been made in understanding AER function in relation to processes critical for limb development: proximal-distal patterning, anterior-posterior patterning, chondrogenesis and apoptosis. By focusing on two major model systems, chick and mouse embryos, we will review recent advances in combination with relevant previous studies in the development and function of the AER.