The focus of this laboratory is to understand the genetic basis of development of form – that is shape, size and proportion during vertebrate development. We focus on the skeleton of the adult fish as a model to understand the genetic basis of growth and proportion that happens during juvenile/adult development. The zebrafish provides a powerful genetic and embryological model to dissect this regulation of late development and is the primary focus of the lab. However, fish are quite varied: they are the most diverse assemblage of all vertebrates with approximately 28,000 species. This diversity provides a unique ability to understand about the variation in genetic and developmental control of the generation of form. We utilize this aspect of fishes to understand the capacity for morphological variation within developmental systems and how this knowledge may help to new therapeutic approaches to repair and regeneration of the skeleton.
Proportion and Growth
We are looking at the coordinated growth regulation that leads to form and function of the skeleton. The scales and dermal rays of the fins are simple models of growth in basically two dimensions – each unit being basically independent in its growth. However, in the skull, the growth of each bone is highly integrated and can lead to coordinated changes of the bones in the skull. Of particular interest is the developmental control of suture patency as changes in this developmental ability is associated with the common birth defect of craniosynostosis. We have uncovered novel means of growth control in regulating proportion. We are investigating the developmental and molecular causes of this control.
Genetic basis of developmental timing events in late development
In our studies, we have uncovered genes that control the timing of development that have critical effects on form and function of the skeleton.
• Cell-ECM interactions.
Several zebrafish mutants we have isolated implicate cellular interaction with the extracellular matrix as a critical component of the timing of skeletal differentiation. We are investigating whether the molecular basis of this control can be mediated as to control differentiation state of bone and cartilage cells.
We all grow old. Some animals show effects of aging early, some later -- some show little sign of aging at all. This life history property is heritable. The fish provides a powerful genetic model to understanding the biology of this process. We identified several zebrafish mutants that show acquired degenerative phenotypes that resemble normal senescence, however occurring in early adulthood. These mutants are being investigated as to how their genes normally function to regulate tissue homeostasis during development and how this regulation is controlled in cases of varied on-set of senescence.
Enders Building, Room 260
300 Longwood Ave.
Boston, MA 02115