Ribs and vertebrae develop from mesenchymal cells located in the ventral somite called the sclerotome. The sclerotome undergoes several morphological changes to form chondrocytes, the cartilage precursors to the vertebrae and ribs. (figure 1)

The signaling molecule Sonic Hedgehog (SHH) is essential for sclerotome development in the mouse. SHH signaling activates gene expression in the sclerotome by activating the transcription factors GLI1, GLI2 and GLI3. GLI2 and GLI3 are thought to be the primary transcriptional mediators of SHH signaling, however their roles in SHH induction of sclerotomal genes have not been investigated. To dissect the function of each GLI in sclerotome development, we have used adenovirus to overexpress GLI1, GLI2 and GLI3 in cultured somitic tissues from mouse embryos. (Figures 2a, 2b)

We find that each GLI preferentially activates a distinct set of SHH target genes, suggesting that the functions of SHH are divided preferentially amongst different GLIs in the somite. We have also examined sclerotome development in embryos lacking functional GLI genes in collaboration with the laboratory of Dr. Chi-chung Hui at The Hospital for Sick Children in Toronto. We find that these genes are absolutely required for proper development of the sclerotome.