HHIP Gene Activity in Bone-Bordering Cells Helps Shape the Skull

Scientists at the Icahn School of Medicine at Mount Sinai showed how the activity of one gene, HHIP, turned on in a newly discovered group of bone-bordering cells, may play an important role in shaping the skull. Their findings were published in Nature.

The team studied how the genetic activity in the cells of the coronal suture changes during early development. To do this, they measured the RNA levels of individual suture cells from embryonic mice about one to three days before the mice were normally born.

Their results suggested that a gene encoding a molecule called hedgehog interacting protein (HHIP) plays a unique and critical role in coronal suture development. The gene was more active in a novel group of mesenchyme cells than it was in osteoblasts. In fact, the scientists saw the opposite trend when they looked at the cells of other sutures. Tracing experiments suggested that after birth the coronal suture osteoblasts were derived from these mesenchyme cells. Moreover, the skulls of embryonic mutant mice that were missing the HHIP gene were shaped differently than those from normal mice. Specifically, there were fewer mesenchymal cells separating the skull bones and the mutant coronal suture was close to fusing.

HHIP is known to inhibit hedgehog activity. To the authors of this study, their results suggest that the HHIP gene reduced hedgehog activity to allow normal development of the coronal suture. They hope that future single-cell genetic studies will continue to give researchers a more thorough understanding of how a skull is shaped under healthy and disease conditions.