During organogenesis, cells face two major challenges. First, progenitor cells need to maintain a balance between self-renewal and differentiation to generate different cell types in a stereotypic manner. Second, differentiated cells need to maintain proper organization to ensure organ functionality. Birth defects are often caused by failure in cellular differentiation, while many human diseases are due to defects in organ maintenance. My lab is interested in understanding the molecular and cellular mechanisms that regulate cell differentiation and tissue maintenance. We use zebrafish as a model system, because molecular and genetic analyses can be combined with high resolution in vivo imaging and large-scale small molecule screens.
We are working on the following three general areas:
(1) Pattern formation during spinal cord development
My lab uses the spinal cord as a model to understand how interactions of different cell signaling pathways (Notch and Hedgehog signaling) drive the precise pattern formation. We have shown that dynamic regulation of Notch and Hedgehog signaling plays an essential role in correct differentiation of neural progenitors (; ). Utilizing novel in vivo reporters, we will visualize cell signaling activities at the single cell resolution, and address how neural progenitors generate different neurons at the correct time and location.
(2) Regulation of muscle maintenance
Skeletal muscles control numerous functions that our bodies constantly perform. Defects in muscle function, for instance muscular dystrophy, have profound consequences. Despite extensive studies in muscles, relatively little is known about how muscle-associated non-muscle cells regulate muscle homeostasis. Our lab focuses on defining the developmental origin and in vivo dynamics of different populations of muscle-associated cells. We have demonstrated that tenocytes (tendon fibroblasts) originate from the sclerotome and play a critical role in maintaining muscle attachment (). We have also defined a population of embryonic muscle progenitor cells that actively contribute to muscle homeostasis and injury repair (). Ultimately, we hope to provide novel insights on how muscle-associated cells communicate with muscle fibers during muscle regeneration and degeneration.
(3) Origin and function of tissue-resident fibroblasts
Fibroblasts are present throughout our bodies. They are the main source of the extracellular matrix (ECM) that provides the structural support. In addition, fibroblasts play pivotal roles in wound healing, inflammation, cancer progression, and in physiological as well as pathological tissue fibrosis. We are interested in addressing where tissue-resident fibroblasts originate from during embryo development, how distinct types of fibroblasts are generated, and how they contribute to tissue homeostasis and regeneration.
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