During vertebrate embryonic development, pairs of metameric units, the somites, bud off at the cranial end of the paraxial mesoderm. The somites soon obtain cranio-caudal and dorso-ventral polarity. Establishment of dorso-ventral and medio-lateral polarity depends on multiple signals from the notochord, neural tube surface ectoderm and lateral mesoderm. The establishment of cranio-caudal polarity in the somite is less well understood. One molecule involved is the Dll1 gene product, a transmembrane protein expressed in the unsegmented paraxial mesoderm and in the caudal half of the somites. We have identified a gene, Uncx4.1, expressed in the caudal half of newly formed somites. It encodes a protein belonging to the paired-related class of homeodomain transcription factors. Uncx4.1 expression is first detected in the entire caudal half of the somites, is later down-regulated in the myotome and dermatome, and is maintained in the caudal sclerotome and its derivatives from which part of the vertebral column will form. Thus, Uncx4.1 may be involved in the establishment and maintenance of segment polarity and in vertebral column formation. Uncx4.1 is also expressed in the first branchial arch, the meso- and metanephric kidney, the central nervous system and the first digit of the forelimb, suggesting control functions of Uncx4.1 in multiple processes of embryogenesis.