A Defined Platform of Human Peri-Gastrulation-Like Biological Fate Patterning Reveals Coordination between Reaction-Diffusion and Positional-Information

Tewary, Mukul 1, 2 ;  Ostblom, Joel 1 ;  Shakiba, Nika 1 ;  Zandstra, Peter 1, 2, 3, 4, 5

1. Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto; 2. Collaborative Program in Developmental Biology, University of Toronto; 3. 3Department of Chemical Engineering and Applied Chemistry, University of Toronto; 4. Terrence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto; 5. Medicine by Design: A Canada First Research Excellence Fund Program, University of Toronto

As the embryo of a multicellular organism develops, different sections of the embryo acquire different identities (or fates). For instance, a specific region of the developing embryo forms the head, other regions give rise to other appendages, internal organs, etc. This biological fate patterning happens in developing embryos in a remarkably robust manner, and the mechanism by which this happens has been a central question in developmental biology for decades. Two prominent biochemical models have provided much insight into the mechanistic understanding of the cell fate patterning and embryonic morphogenesis: reaction-diffusion (RD) – proposed by Alan Turing, which suggested that positive and negative diffusible regulators of signaling can give rise to self-organized fates of complex patterns within a developing tissue; and positional information (PI) – proposed by Lewis Wolpert, which suggested that developing tissues require prior asymmetries of signaling molecules, and this asymmetric distribution of signaling molecules pattern fates as a function of both signaling threshold and induction time. Although there are vast amounts of evidence to support both these models, they have historically been thought of as being mutually exclusive.