Correct innervation of peripheral muscles by spinal cord motoneurons is required to coordinate body movements in vertebrates. Hox proteins play an important functional role in achieving this innervation by specifying neuronal fates along the anteroposterior axis of the developing spinal cord. However, the mechanisms that generate Hox gene expression patterns are poorly understood. Here (p. 929), Denis Duboule and colleagues use tiling array-based transcriptome analyses and targeted deletions in vivo to investigate the control of HoxD gene transcription in the developing mouse spinal cord. They report that there are two distinct blocks of HoxD transcription that are regulated independently and that define two general expression territories. These territories, they show, are associated with the future nerve plexii at the brachial and lumbar levels. Given these and other results, the researchers propose that the establishment of spatial collinear HoxD domains in the developing mouse spinal cord involves the bimodal control of HoxD gene transcription by two independent ‘enhancer mini-hubs’.