Ashley RG Libby

In development, gene regulatory networks interpret extrinsic signals to drive cell diversification and tissue generation. This is remarkable because it requires tight coordination of gene expression in time and space despite dynamically changing environments. The Libby Lab asks how dynamic gene regulation coordinates with/can be directed by morphogenesis. We focus on the formation of the neural tube, which gives rise to the central nervous system. Neural tube formation is a complex process where progenitors undergo lineage fate determination alongside population level morphogenic events. When this process is disrupted, it results in neural tube defects like spina bifida, affecting 1 in 2,500 children worldwide. Causes of spina bifida remain largely elusive, where a combination of environment and genetic predisposition affects the closure of the neural tube. Therefore, the Libby lab seeks to fully characterize neural tube formation to both untangle pathological drivers of spina bifida, but also to illuminate global mechanisms that relate the feedback between signalling and morphology. By combining in vivo CRISPR screening in chick embryos with in vitro human stem cell models, we investigate development across molecular, cellular, and tissue scales. This integrated approach allows us to uncover fundamental mechanisms governing organ formation and informs strategies for tissue engineering and regenerative medicine. Ongoing projects focus on two major themes: First, we investigate how transcriptional responses are connected to environmental signals. Neural tube progenitors rely on bivalently marked genes to rapidly activate transcription in response to morphogenic cues, but the epigenetic machinery and limits of this responsiveness remain unclear. Second, we study how developing tissues buffer against changing environments. The neural tube forms through distinct morphogenetic routes at different developmental stages, yet reliably produces the same tissue. Understanding how robustness is achieved may reveal general principles of development and guide the construction of tissues in vitro.