OriSha · Engineering the Origin of Human Shape: Defining Patterns and Axes in the Early Stage of 3D Pluripotency

How an organism takes shape is a longstanding challenHow an organism takes shape is a longstanding challenge in modern biology and medicine. Understanding how, during the 3D embryo development, different molecular players, such as genetic programs, morphogens, and forces work together to build the shape of the body is still far to be understood, especially for humans. In recent years, some progress has been made to understand the inaccessible state of human development through models of human embryos derived from pluripotent stem cells. Although they brought very exciting findings, this approach failed in reconstructing the dynamic of the proper axes formation and 3D spatially ordered structure of tissues. OriSha will provide a ground-breaking technology to control over time and space the early stage of human shaping by modulating in an in vitro model the biochemical and biophysical properties of the microenvironment. I will develop a hydrogel-microfluidic system to accurately and dynamically deliver liquid instructive signals coupled with 3D shape-controlled organoid technology to guide the geometry during morphogenesis and recapitulate the very early and inaccessible stages of human embryo development. With this technological approach, I will instruct gradients of signalling molecules by imposing morphogens into the targeted tissues with unprecedented temporal and spatial resolution. To demonstrate the unique potential of this approach I will focus my interest on the development and morphogenesis of the neural tube that is the primordium of the central nervous system. Thanks to my cutting-edge approach, for the first time I will have the opportunity to investigate the correlation between the spatio-temporal dynamics and the 3D tissue patterning and self-organization during human embryonic development. The proposed project has the potential to become the new gold-standard for in vitro human developmental modelling, completely overcoming the need of human embryos.