The paired homeobox gene Uncx4.1 specifies pedicles, transverse processes and proximal ribs of the vertebral column

The axial skeleton develops from the sclerotome, a mesenchymal cell mass de rived from the ventral halves of the somites, segmentally repeated units lo cated on either side of the neural tube. Cells from the medial part of the sclerotome form the axial perichondral tube, which gives rise to vertebral bodies and intervertebral discs; the lateral regions of the sclerotome will form the vertebral arches and ribs. Mescnchymal sclerotome cells condense and differentiate into chondrocytes to form a cartilaginous preskeleton tha t is later replaced by bone tissue. Uncx4.1 is a paired type homeodomain tr anscription factor expressed in a dynamic pattern in the somite and sclerot ome. Here we show that mice homozygous for a targeted mutation of the Uncx4 .1 gene die perinatally and exhibit severe malformations of the axial skele ton. Pedicles, transverse processes and proximal ribs, elements derived fro m the lateral sclerotome, are lacking along the entire length of the verteb ral column. The mesenchymal anlagen for these elements are formed initially , but condensation and chondrogenesis do not occur. Hence, Uncx4.1 is requi red for the maintenance and differentiation of particular elements of the a xial skeleton.