Animal development involves the precise control of cell division, cellular quiescence, cell fate specification, differentiation, and morphogenesis. All these processes are controlled by cell signaling and genetic regulatory mechanisms whose components and interactions have been shaped by evolution for maximum fitness. We study genetic regulatory networks in C. elegans that are responsible for orchestrating temporal patterns of developmental events during larval development, with an eye on uncovering principles and mechanisms that ensure robust coordination of developmental progression throughout the animal. We will expand on our previous studies of the roles of microRNA pathways in developmental robustness to investigate mechanisms coupling microRNA biogenesis to developmental progression under conditions of stress. We will continue to explore the roles of microRNAs and other factors in coordinating transcriptional and post-transcriptional regulatory mechanisms for robust temporal control of development, particularly in the context of deeply conserved microRNAs and microRNA target motifs. We will investigate the relationship of the periodic components of worm development -- particularly molting and larval diapause ? to the progressive advancement of stage identify and cell fate progression, with the aim of testing hypotheses for how cell divisions and cell fate transitions are coordinated on the organism level.
All complex multicellular animals, including worms and humans, develop from embryo to adult, and conduct the essential tasks of maintaining and repairing their tissues, using mechanisms that evolved long ago in our common ancestors. Animal development and tissue homeostasis is remarkably resilient, occurring essentially error-free in spite of the inevitable physiological and environmental stresses of everyday life. Through acquiring a deep understanding of the fundamental molecular mechanisms responsible for the normal resiliency of development and tissue homeostasis, we can learn how to better address diseases wherein that resiliency breaks down, such as cancer and neurodegeneration.
