Research

The objective of the Dudley laboratory is to define the molecular mechanisms that regulate morphogenesis and tissue patterning in the early vertebrate embryo. In particular, we are interested in determining how signaling events regulate cell behaviors and how changes in cell behavior alter embryonic form. We use development of the skeleton in the chick and mouse as primary model systems and our experimental approaches include classical embryology, molecular biology, biochemistry, proteomics, genomics, imaging, and in vitro models. The long-term goal of our research is to promote the development of novel therapeutic approaches for regeneration following catastrophic tissue loss due to injury or disease.

Current projects are focused on the initial steps in forming the cartilage skeleton of the limb and the regulation of long bone growth by the cartilage growth plate.

Limb skeleton formation
The vertebrate limb bud is composed of a mound of mesenchyme enveloped in a jacket of ectoderm. Patterning events lead to the formation of cell condensates in the mesenchyme that form cartilage elements of distinct morphologies along the proximo-distal (shoulder-finger) and anterior-posterior (thumb-little finger) axes. We previously showed that the patterning information is present in the early limb bud before overt cartilage formation [link to Dudley et al., 2002] however the mechanism of patterning and the signals that promote local cell condensation are currently unknown. Our laboratory is actively seeking to further define the system(s) that pattern the early limb skeleton.

Cartilage growth plate function
Growth of long bones is controlled via regulation of chondrocyte maturation in the growth plate cartilage that is composed of four zones of cells with distinct morphologies. Resting chondrocytes comprise a population of progenitor cells that reside at the ends of the bones and exhibit a low level of cell cycle activation. Maturation begins with formation of discoid proliferative chondrocytes that display increased cell cycle activity. After many rounds of division, the cell cycle is downregulated and the cells change shape (prehypertrophic chondrocytes). Subsequently, prehypertrophic chondrocytes enlarge to form hypertrophic chondrocytes that secrete the extracellular matrix protein collagen X and undergo cell death. A major effort in our laboratory is to define the molecular pathways that control zone specific morphologies and to determine the role these distinctions play in growth plate function.