Keck School of Medicine
- Developmental Biology
- Evolutionary Biology
- Stem Cell Biology
- Cell Cycle
- Growth & Proliferation
Research OverviewThe laboratory asks fundamental questions in bio-medical research. The focus of researches is morphogenesis, i.e. how cells are assembled into functional forms. We are concerned with the principles that determine the specific number, size and shape of different organs. This is an important process, as there is much to learn about the principles that can guide stem cells to form specific tissues and organs required for medical treatment. Our approach is to ask Nature how she does it - using the feather as a Rosetta stone to decipher these principles, because of the distinctive forms of feathers and interest in the evolution of flight. This unique model has allowed us to make several major impacts in the field of morphogenesis and develop interesting interfaces with scientists in different disciplines.
A. Stem cells and regeneration.
A feather has the most robust regenerative power and regeneration is part of its physiological process, yet no one knows where feather stem cells are. Equipped with modern approaches, Dr. Chuong's laboratory set out to hunt for feather stem cells, which were found in an unexpected location: unlike hair bulge stem cells, they were found within the feather follicle. Feather and hair follicles actually form as a result of convergent evolution and they have similar as well as different ways of "managing" their stem cells during molting/regeneration. This novel piece of work will be published in Nature (Yue et al., Dec 15, 2005). Indeed different organs have different ways of handling stem cells and regeneration. The different ways of managing their stem cells may be the basis of their different regeneration abilities.
The laboratory now focuses on the engineering of ectodermal organs and the use of hair follicles as the source for adult stem cells (Jiang). The laboratory also studies human wound healing in collaboration with Dr. Tai Lan Tuan of Department of Surgery, Dr. Woodley of Dermatology and Dr. Garner of Burn unit. Chuong laboratory also uses animal model such as lizard tails (which regenerate) to learn whether it is possible for human limbs or digits to regenerate.
B. Signaling molecules in epithelial-mesenchymal interactions during skin morphogenesis.
Dr. Chuong's laboratory uses chicken embryos as the model for skin morphogenesis, bringing studies in experimental embryological studies up to modern day biology by giving molecular explanations and new meanings to classical studies. In 1998, he edited The Molecular Biology of Epithelial Appendage Morphogenesis (Landes Bioscience; Chuong edit, 1998) developing the concept that ectodermal organs over the body surface are variations of a common theme (these organs share proto type molecular pathways). This book was recognized as an inspiration in the field, as it provides an insightful vision and helps catalyze the molecular signaling research in the mammalian hair field. In subsequent studies, he also demonstrated that by tuning the balanced activity of a single molecular pathway, it is possible to change the number, shape, size and even phenotypes of various ectodermal organs (Plikus et al., 2003, 2005).
C. Biological mechanisms of pattern formation: Self-organization
Because of the exquisite hexagonal pattern of feather buds, it has long been suggested that cells follow molecular codes to forms bud or interbud regions. With a novel reconstitution assay developed in his laboratory, Dr. Chuong showed that in the beginning all cells have an equal chance to go to bud or interbud regions. The patterning process is a stochastic event involving reaction diffusion and competitive equilibrium, not a readout of preexisting molecular codes. Dr. Wei Min Shen, USC information Science Institute, was seeking clues that will allow multi-robots form different formations by themselves. Together, they developed a digital hormone model that can be applied to the self-organizing behavior of both robots and live cells (Shen et al., 2004; Jiang et al., 2004). We now try to identify molecular basis of these processes (Lin).
We also study hair cycling and pattern formation and skin domains on the mouse (Plikus).
D. Evolution and development of feathers
The transition from reptile scales to avian feathers is a multi-step process achieved over 50 million years of selection. The earliest drive is likely to be thermoregulation. Skin appendages start to elongate and form branches to trap air. These branches were originally randomly arranged. Novel developmental mechanisms later evolve to make them bilateral symmetry, allowing the formation of a two dimensional vane that can be used for communication display. Subsequent formation of bilateral asymmetric feather vanes makes the wing feathers adapt to aerodynamic requirement. Without these critical events in feather morphogenesis, birds will not be able to fly. To study these events, Dr. Chuong's team developed a novel plucking/regeneration/gene mis-expression assay in adult chicken, which allows them to search for molecular pathways involved in these processes. This new field was published in Nature (Yu et al., 2002), and he was invited to be the guest editor for J. Expt. Zoology and co-edit a special issue on the "Development and Evolution of Amniote Integuments" (Chuong and Homberger edit, 2003). The special issue covered the adaptations of the integument from aquatic to land environment and to the flight in the sky, providing the field with a platform to discuss the definition of feathers.
E. Molecular shaping of the beak.
With his passion to search for the origin of research subjects, Dr. Chuong went to dig fossils with Chinese paleontologists in a remote site of Northern China (Jehol Biota) where several feathered dinosaurs have been discovered. He joined the analyses of these early "protofeathers," and is the corresponding author of the team that discovered pigeon-sized Longirostravis, the earliest wading birds (120 million years old) with a long beak, 10 conically shaped beaks, and elongated legs (Hou et al., 2004). The ecological driven change of beak shapes during evolution prompted him to also look further into molecules mechanism behind the shaping of the beaks. Evolution of beak diversity is a classical question raised by Darwin after he was inspired by the diverse beak shapes of Galapagos island finches. In order to have a workable model, Dr. Chuong questioned why chicken and duck beaks were made differently and found that a simple change in topological arrangement of growth zones is sufficient to lead to major consequences in morphological differences. His team was able to convert the conical shaped chicken beaks into diverse beak shapes that mimic those found in Nature, and his work was later published in Science (Wu et al., 2004). This project is mainly carried out by Dr. Ping Wu.
F. Formation of epithelial organs: liver, mammary gland
We now study signaling involved in the early development of chicken liver. We study morphogenetic activities during tooth development (Plikus). We also study epithelial-mesenchymal interactions in mammary gland development (mainly by Dr. Widelitz). How this is related to breast cancer is studied in collaboration with Dr. Malcom Pike and Dr. Anna Wu.