Coordinating decision-making and the cell cycle: the role of signal dynamics (360G-Wellcome-339191_Z_25_Z)

A limited set of signalling molecules drive embryonic cells to self-organise, pattern tissues and construct the entire body plan. Mutations that corrupt accurate signal interpretation are common drivers of human disease, however, embryonic development remains highly robust to these perturbations. Using a combination of quantitative imaging approaches and optogenetics, my aim is to uncover the basic design principles of dynamic signal interpretation and understand how the embryo coordinates tissue growth and cell decision-making, using Ras-Erk signalling in craniofacial patterning as a paradigm. Tissues that contribute to craniofacial development display differential sensitivity to the same perturbed signal in a family of developmental disorders, known as RASopathies. I will combine imaging approaches with whole embryo single-cell RNA-seq to determine what aspects of craniofacial development (signalling, gene expression, cell numbers) are sensitive to perturbation in the context of disease. Our ability to investigate the role of signal dynamics in embryonic development and disease has been limited by technology. However, I and others have pioneered new biosensors that enable the tracking of single-cell signalling and decision-making in vivo. Using zebrafish and Drosophila embryos as optically accessible models, I will reveal how tissues interpret normal and corrupted signals and identify buffering mechanisms that safeguard development.