Research 

We study disorders that affect skeletal development.

Our research is directed at two areas that contribute to these anomalies: 1) errors in skeletal patterning and 2) errors in skeletal formation. 

A. Paraxial mesoderm patterning and somitogenesis.

The blue print for the segmented vertebral column is established from transient developmental tissues known as somites.  A well orchestrated series of developmental events ensures the correct spatial and temporal formation of these tissues. Somites provide the progenitor cells that form the bones of the vertebral column and ribs, as well as the trunk musculature and dermis. Somites also provide positional information that guide migration of spinal nerves. Disruption in the timing and formation of the somites can lead to vertebral malformations included congenital scoliosis.  We study the mechanisms of how positional information is established to form of these segmentation structures using zebrafish and mouse genetic models. In addition we use mouse embryonic stem cells to study the cell and molecular biology of paraxial mesoderm differentiation.

B. Formation of the skeleton

The mammalian skeleton forms through two developmental processes:  intramembranous ossification and endochondral ossification. Intramembranous ossification processes form the flat bones of the skull and occurs through the direct differentiation of mesenchymal progenitor cells directly into bone forming osteoblast cells. In contrast, the majority of the skeleton forms through endochondral ossification events whereby mesenchyme progenitors cells transition through a cartilage intermediate, that facilitates growth and patterning, before being replaced by a bony matrix. This developmental pathways is tightly regulated and disruption in its ordered progression can have profound developmental defects to the skeleton.  The transcription factors Foxc1 and Foxc2 are critical regulators of both ossification pathways. Our laboratory uses conditional mouse mutants to study the role of Foxc1 and Foxc2 in regulating endochondral ossificiation pathways. In addition we use genome-wide approaches (ChIP-seq and RNA-seq) to identify genes under the regulatory control of Foxc1 and Foxc2 that are needed to correctly form the skeleton.