Fred Berry

My laboratory is interested in understanding how specific skeletal elements such as the limbs and the spine are patterned to acquire their characteristic shape and grow correctly. We focus on the gene regulatory networks controlled by the transcription factors Foxc1 and Foxc2 that guide these developmental processes. Our research activities are divided into the following area:

1. 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. Foxc1 and Foxc2 are critical regulators of both ossification pathways. Our laboratory focuses on the role of Foxc1 and Foxc2 in endochondral ossification. In addition we use genome-wide approaches (ChIP-seq and RNA-seq) to identify genes under the regulatory control of Foxc1 and Foxc2 needed to correctly form the skeleton.

2. Paraxial mesoderm patterning and somitogenesis.
Somites are transient developmental tissue that give rise to the bones of the vertebral column and ribs, as well as the trunk musculature and dermis. The structures arise from paraxial mesoderm that condenses into these spherical somite. We study the mechanisms leading to the formation of these structures. In addition we study how positional information within them is established and maintained. This information is needed to correctly form the bones of the vertebral column and to innervate the spine.

3. Transcription networks regulating cells fate decisions.
Changes in gene expression are a hallmark of cell differentiation. Many of such genes expressed will guide cells along this developmental path and will also contribute to the final phenotype. We are interested in understanding how transcription factors act to specify these gene regulatory networks that lead to cell differentiation events. To study these processes we use mouse embryonic stem cells targeted to differentiate towards specific lineages and monitor how changes in gene expression can influence differentiation outcomes.