Establishment of Hox vertebral identities in the embryonic spine precursors

The vertebrate spine exhibits two striking characteristics. The first one is the periodic arrangement of its elements-the vertebrae-along the anteroposterior axis. This segmented organization is the result of somitogenesis, which takes place during organogenesis. The segmentation machinery involves a molecular oscillator-the segmentation clock-which delivers a periodic signal controlling somite production. During embryonic axis elongation, this signal is displaced posteriorly by a system of traveling signaling gradients-the wavefront-which depends on the Wnt, FGF, and retinoic acid pathways. The other characteristic feature of the spine is the subdivision of groups of vertebrae into anatomical domains, such as the cervical, thoracic, lumbar, sacral, and caudal regions. This axial regionalization is controlled by a set of transcription factors called Hox genes. Hox genes exhibit nested expression domains in the somites which reflect their linear arrangement along the chromosomes-a property termed colinearity. The colinear disposition of Hox genes expression domains provides a blueprint for the regionalization of the future vertebral territories of the spine. In amniotes, Hox genes are activated in the somite precursors of the epiblast in a temporal colinear sequence and they were proposed to control their progressive ingression into the nascent paraxial mesoderm. Consequently, the positioning of the expression domains of Hox genes along the anteroposterior axis is largely controlled by the timing of Hox activation during gastrulation. Positioning of the somitic Hox domains is subsequently refined through a crosstalk with the segmentation machinery in the presomitic mesoderm. In this review, we focus on our current understanding of the embryonic mechanisms that establish vertebral identities during vertebrate development.