The mammalian body plan blueprint, an in vitro approach

ended

The development of an embryo requires the spatially structured emergence of tissues and organs. This process relies on the early establishment of a coordinate system in the form of three orthogonal axes that act as a reference for laying down the body plan, a template for the organism. Genetic analysis of this process has revealed an underlying transcriptional blueprint that links the coordinate system and the body plan. However, the way in which the gene products contribute to the emergence of the body plan remains an open question. A reason for this is that this process involves feedbacks and integration between the activity of Gene Regulatory Networks (GRNs) and the mechanics of multicellular ensembles, and that probing this relationship is experimentally challenging. In the case of mammalian embryos, which are particularly important as models for human development, our gaps in knowledge of these events are larger than in other organisms. This is partly due to the challenges associated with uterine development but also, and increasingly, because of the cost of mice and the difficulty of obtaining large numbers of embryos, as required for mechanistic experiments. In this project we shall use gastruloids, a novel and versatile Pluripotent Stem Cells based experimental system that we have developed for the study of mammalian development, to gain insights into the molecular and cellular basis underlying the emergence of the mammalian body plan. Gastruloids lack anterior neural structures and over a period of five days become organized in the fashion of a midgestation mouse embryo. We shall use the experimental versatility of the Gastruloid system to probe into the functional relationships between the mechanical activities of multicellular ensembles and the dynamics of GRNs that underlie the emergence of the mammalian body plan.