The process by which a fertilized egg gives rise to a fully-formed multicellular individual is part of the broad field known as developmental biology. Development is concerned with the life history of cells in general----including the complex ways that genetic information is translated into organismal structure and function. This includes the molecular mechanisms by which cells specialize and become different from one another, and the ways that shape, form and pattern arise in each generation.
The fundamental question that drives my research is: " How a single cell, the fertilized egg, develops into an animal with thousands of distinct type of cells - muscle cells, neurons, epidermal cells, blood cells, and so on?" We are particularly interested in the cellular and molecular mechanisms that control the differentiation of muscle and skeletal cells during embryogenesis. Specifically, we use zebrafish as a model system to uncover gene function involved in muscle and bone development and muscle repair.
Zebrafish as a Model Organism
Model organisms, also known as model systems, are animals or plants that are well characterized and amenable to laboratory study. Many important insights into muscle and bone formation have come from studies of animal models, such as mice, chick, and fish. These studies have provided fundamental information about genes that regulate the development of bone and muscle cells. It is apparent that most of the genes or genetic pathways that control muscle or skeleton formation are highly conserved in vertebrates, and signaling molecules required for embryonic muscle/skeletal development are also important in adulthood.
Zebrafish provides unprecedented opportunities for the study of vertebrate development for several reasons: the genome of this organism is well characterized, the animal can be easily reared in laboratory settings, and techniques have been developed for genetic manipulations involving introduction of modified genes and manipulation of the expression of specific genes of interest. Also of great importance, the embryo remains translucent throughout much of its development, so that it can be studied in detail under the microscope. Such study includes ingenious methods that have been developed for tagging the protein products of specific genes with fluorescent markers.
Our laboratory is focused on the genetic regulation of muscle and bone development. Skeletal muscle and bone are specialized tissues that make up the muscle/skeletal system that confers multiple mechanical and biological functions, such as providing physical support for our body, protecting vital organs (e.g., brain, lung). The important function of muscle/skeletal system can be easily recognized in day-to-day life, where millions of people suffer from muscular and skeletal diseases such as muscular dystrophy, or osteoporosis. The better understanding of the regulation of muscle and bone formation during embryogenesis will provide new insights into the molecular mechanisms of muscle/skeletal diseases and give rise to novel strategies for new drug design as well as alternative therapeutic approach using embryonic stem cells.
The research objective of my laboratory is to use zebrafish as a model system to identify the genetic program involved in muscle and skeleton formation. Our research focuses on the Hedgehog and BMP (bone morphogenetic protein) signaling pathways that play important roles in muscle and bone development (Du et al., 1997; Haga et al., 2009). Our recent studies are focused on the genetic regulation of muscle fiber maturation, the assembly of sarcomeres. We demonstrated that Smyd1, a member of the Smyd family and Hsp90a1 play vital roles in sarcomeres assembly (Tan et al., 2006; Du et al., 2008). Knockdown of Smyd1 or Hsp90a1 resulted in defective thick and thin filament organization in skeletal and cardiac muscles. Results from these studies have potential application in clinical research, because knowledge gained from these studies may lead to the design of new genetic screenings for muscle diseases, and development of new drugs that could regulate the activities of these factors for treatment of muscular and skeletal diseases, and new strategies to instruct differentiation of ES cells specifically into muscle or bone cells for cell-based therapy.
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