Human PAX gene expression and development of the vertebral column.

The human gene HuP48 is a member of the PAX family of developmental control genes. Common to all members of this family is a highly conserved DNA sequence, the paired box sequence. In several species, paired box-containing genes function in normal embryonic morphogenesis. To investigate the possible involvement of PAX genes in the development of the human skeleton, the authors analyzed the expression of the paired box-containing gene, HuP48, in the fetal human vertebral column. In addition, the authors sequenced the paired box region of HuP48 from patients with congenital vertebral anomalies associated with Klippel-Feil syndrome. Using in situ hybridization, it was observed that HuP48 is expressed in a segmented pattern in the developing spine, specifically in the cells of the intervertebral disks of seven- to eight-week-old fetuses. At this stage in development, HuP48 expression appears to be restricted to the vertebral column. The pattern of expression of HuP48 indicates that it plays a role in establishing the segmented pattern of the vertebral column, perhaps by helping to establish and/or maintain, or both, a border between two different populations of cells, those of the prevertebrae and those of the intervertebral disks. Analysis of HuP48 paired box sequences in genomic DNA obtained from patients with congenital segmentation anomalies revealed no mutations in this highly conserved sequence.