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The fundamental question we are trying to answer is how the coordinated cell movements are regulated during embryogenesis. It is a very complex process since the “ground” cells travel on is also undergoing constant rearrangement and growth. We use neural crest as a model to study the mechanisms of cell migration during embryonic development. The neural crest is a vertebrate innovation, comprised of highly migratory stem-like cells that give rise to a wide variety of tissue and cell types, including craniofacial bones and cartilages, connective tissue in the heart, enteric nervous system in the gut, and pigment cells all over the skin. Defects in their proliferation, migration, differentiation, or survival lead to numerous diseases and birth defects, including craniofacial and heart malformations as well as different types of cancer. We are interested in understanding neural crest cell migration at a mechanistic level, focusing on the role of actin cytoskeletal machinery that powers cell locomotion. Despite the rich knowledge of how actin filaments mediate cell motility in culture, little is known about the dynamic regulations of actin cytoskeleton during cell migration in living embryos. Our lab is investigating the roles of novel actin cytoskeletal regulators (ACRs) during neural crest migration and actin dynamics, as well as the functional and physical interactions between different ACRs, with the goal of integrating such knowledge into a comprehensive and dynamic actin regulatory network during cell migration in vivo. Although this work focuses on neural crest migration, it promises to provide insights and build a foundation for our general understanding of the mechanistic control of cell migration, both during embryogenesis and in adult homeostasis.