Multi-contrast dynamic optical imaging to advance live developmental biology

PROJECT SUMMARY/ABSTRACT Imaging is essential for the study of developmental biology. In particular, optical imaging, with its high resolution, has been making revolutionary impacts on our understanding of biological development. To a large degree, the imaging capability defines what can be studied in developmental biology. From 2D to 3D, from static to dynamic, advancements in optical imaging have enabled us to connect molecular genetics with volumetric morphogenesis and have marked an exciting era of studying the underlying mechanisms in the context of dynamic developmental process. Biological development is fascinating. From a single cell to a multi-billion cell system, cells with virtually identical genes acquire different fates and are able to exhibit diverse behaviors and functions. To elucidate this complex process, to dissect the mechanistic link between genotypes and phenotypes, and to define the roles of biophysical, biochemical and biomechanical factors in the organismal growth and physiology, multi-contrast imaging, capable of probing and bridging a wide range of biological information, is imperative and holds the promise for the next revolution in the study of developmental biology. Understanding of development requires different model systems, each with advantages in pursuit of specific questions. Among these, the mouse is the premier mammalian model with well-established genetic tools for mutagenesis strategies and modeling of human diseases. Studies on mice can produce insights that are highly relevant to human; however, many important developmental questions cannot currently be studied using the mouse model, largely because it is difficult or impossible to image the required information. This lack of proper imaging approach acts as a critical hurdle, especially for live studies of the developing cells, tissues and organs, which are essential for a comprehensive understanding of development. The goal of this research program is to establish a multi-contrast, high-resolution dynamic imaging platform to advance live developmental biology, especially in the mouse model. Our technical innovations are based on optical coherence tomography (OCT), a high-speed imaging modality with micro-scale resolution and millimeter-level depth. Recently, we demonstrated live 4D (3D+time) structural and functional OCT imaging of mouse embryos at a variety of time scales, revealing unprecedented mammalian developmental dynamics. Building on this, we will pursue three projects to pioneer 3D-registered and integrated structural, functional, molecular and biomechanical contrasts for live and dynamic studies of mammalian development. This research program will generate a new frontier in the study of developmental biology and will make a major step forward in understanding of mammalian development.