Bone and cartilage provide animals with support and protection. Cartilage is important because it provides the scaffold to allow bone formation during embryonic development. Cartilage is formed first, and most of it is then replaced by bone. Cartilage is also important in adults, where it resides in a number of places including the nose, the ear, and the joints. Degradation of cartilage at the joints results in arthritis, a major disease that leads to disability. We study cartilage development in the embryo, which helps us to understand why diseases such as arthritis arise.

Specifically, we study the cell fate determination process and how the intracellular factors regulate cartilage development. Imagine yourself as a cartilage progenitor cell—you will have many decisions to make while you mature. How do you decide to become a cartilage cell or a muscle cell? You may receive signals from the surrounding tissues. How do you interpret such signals? Once you are a cartilage cell (chondrocyte), how do you decide whether to become a cell in the vertebra or the rib? As a young cartilage cell, you will experience a series of developmental stages in your life (e.g. proliferation stage, maturation stage). How do you decide how long you should stay in each stage?

We use somites as a model system to understand such decision-making processes. Cartilage of the vertebra and the ribs is derived from somites. Sonic hedgehog (Shh), a secreted protein, instructs the somite cells to establish cartilage cell fate. We have found that the signal Shh is interpreted by two intracellular transcription factors, Sox9 and Nkx3.2, within the somite cells. Together with Bone Morphogenetic Proteins (BMP), Sox9 and Nkx3.2 form a positive-regulatory loop and mimic the activity of Shh in promoting cartilage formation.

As Sox9 and Nkx3.2 are so important for cartilage formation, we will focus our research on the regulation of these two transcription factors in cartilage progenitor cells. Using a combination of approaches in embryology (e.g. tissue isolation, in vivo gene delivery and in situ hybridizations), molecular biology and protein biochemistry, we hope to uncover the mechanisms of the decision-making process during cartilage development, and contribute to cartilage regeneration technology.