Form and function of embryogenesis and pathogenesis
Many diseases can be considered as a failure of development. Investigating the borderland of embryology and pathology is a fundamental method for learning the rules of development. My group investigates the fundamental principles that guide how cells self-organize through collective interactions to bring about changes in embryonic form and function. By integrating advanced molecular, imaging, single cell transcriptomics, and statistical approaches, we study how molecules work together to control the timing and the spatial pattern of cell differentiation in developing tissues and stem cell systems.
Germ cells retain the capacity for both totipotency and immortality. They link one generation to the next and so are fundamental to the survival and evolution of living organisms. Germ cells migrate during the critical process of gastrulation, when the three primary germ layers-ectoderm, endoderm, and mesoderm—are form and the primary body axes are established. We are taking an interdisciplinary approach to studying primordial germ cell (PGC) development in the context of gastrulating embryos by combining the power of molecular genetics with advanced optical imaging within living embryos. Transgenic quail that ubiquitously express fluorescent proteins provide a novel amniote model system that permits investigations in living embryos with unprecedented spatiotemporal resolution. The quail epiblast, like the human epiblast, flattens out to form a disc, from which the primitive streak arises at one end. The dynamics of spatial relationship between lineages in the gastrulating human remain unexplored. Our studies address outstanding questions fundamental to PGC development and early embryogenesis including when, where, and how they are specified, how balance their need to move with their need to proliferate, and how they move in and out of the living embryo. PGCs have important therapeutic implications for the field of reproductive medicine; however, further development of tools and studies of the mechanisms to specify and maintain germ cell niches in diverse systems are essential for an improved understanding of germline development and reproductive health.