Investigating the mechanisms for building the embryonic body plan: harnessing a paradigm for cell differentiation

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The fundamental job of embryo development is to build the adult body, made of hundreds of different kinds of cell, starting with a few identical cells, at the right place and time. If we were to know precisely how this happens, we could control this process in a dish to generate cells that could be transplanted to repair damage in degenerative disease and injury. In animals with a backbone, all the cell types except those in the head form from a set of unspecialised cells (neuromesodermal progenitors) at the tail end of the embryo, progressively laying down the spinal cord, muscles and skeleton in sequence from neck to tail. During this period, cells have to decide between alternative types and typically have a greater potential than their eventual fate (a property called 'plasticity') and only later irreversibly commit to a given cell identity. We have found that neuromesodermal progenitors mature over time as they produce the neck, then the ribcage, lower vertebrae and optional tail. We propose that this maturation process is important for the different cell types formed along the head-to-tail axis. We have found conditions to culture these cells, and will test molecules in culture that our previous work has suggested is important for making these progenitors mature. We will check if the cell types formed from progenitors at different stages of maturity have different functions. We will also find out how cells commit to given cell types by studying plasticity in individual cells, and, in parallel cells, the different genes that are active in cells that can change identity and those that do not. We will test whether loss or gain of any of these differentially-active genes changes cells' ability to commit to their fates.