A Switch Between Topological Domains Underlies HoxD Genes Collinearity in Mouse Limbs

Collinearity Cracked in Tetrapod Limbs During limb development, the time a nd place of Hox transcription are fixed by respective gene position within the gene cluster. Andrey et al. (p. 1234167 ; see the Perspective by Rodrigues and Tabin ) found that this enigmatic property results from the opposite and successive actions of two large regulatory landscapes located on either side of the mouse Hox locus. In the early phase, one of these topological domains regulates transcription in the proximal limb until a switch occurs toward the other topological domain, which takes over the regulation in the distally developing digits. As a side effect of this antagonistic regulatory strategy, cells in-between have lessened Hox transcription, which generates the wrist.