Limb development: A paradigm of gene regulation

The limb is a commonly used model system for developmental biology. Given the need for precise control of complex signalling pathways to achieve proper patterning, the limb is also becoming a model system for gene regulation studies. Recent developments in genomic technologies have enabled the genome-wide identification of regulatory elements that control limb development, yielding insights into the determination of limb morphology and forelimb versus hindlimb identity. The modulation of regulatory interactions-for example, through the modification of regulatory sequences or chromatin architecture-can lead to morphological evolution, acquired regeneration capacity or limb malformations in diverse species, including humans.