Engineering pattern formation and morphogenesis

Abstract

The development of natural tissues, organs and bodies depends on mechanisms of patterning and of morphogenesis, typically (but not invariably) in that order, and often several times at different final scales. Using synthetic biology to engineer patterning and morphogenesis will both enhance our basic understanding of how development works, and provide important technologies for advanced tissue engineering. Focusing on mammalian systems built to date, this review describes patterning systems, both contact-mediated and reaction-diffusion, and morphogenetic effectors. It also describes early attempts to connect the two to create self-organizing physical form. The review goes on to consider how these self-organized systems might be modified to increase the complexity and scale of the order they produce, and outlines some possible directions for future research and development.

Synthetic living machines: A new window on life

“…In one set, the main objective is to reconstitute or emulate developmental mechanism in vitro either in cell lines with no developmental potentials or in stem cells with unique self-organization properties. For instance, genetic circuits and artificial cell-cell communication were engineered to induce cell sorting and pattern formation in cell lines ( Davies and Glykofrydis, 2020 ). Exploiting the innate self-organization properties of stem cells could also generate mimetic of early developmental tissues or later human organogenesis in vitro .…”

“…Hence, understanding and engineering different modes of communication and patterning in prokaryotic and eukaryotic cells have been a quest for developmental and synthetic biologists ( Basu et al., 2005 ; Davies and Glykofrydis, 2020 ; Green and Sharpe, 2015 ; Levin and Martinez Arias, 2019 ; Matsuda et al., 2012 ; Weber et al., 2007 ; You et al., 2004 ). Inspired by pioneering works by Steinberg (1963 ), seminal studies used cadherins to probe differential adhesion, cell sorting, and pattern formations ( Cachat et al., 2016 ; Davies and Glykofrydis, 2020 ). Combining cadherin-mediated cell sorting with artificial cell-cell communication also produced multi-layer self-organization and multicellular patterning ( Toda et al., 2018 , 2020 ).…”

Synthetic cell–based materials extract positional information from morphogen gradients

“…Biological development-the generation of a complex, differentiated organism starting from a single cell-is a notable example of selforganization in biology that has inspired chemists, materials scientists, molecular programmers, and synthetic biologists alike to envision autonomously developing, self-differentiating, and self-sustaining biomimetic systems (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Newly available techniques such as three-dimensional (3D) printing of soft materials have opened up the possibility to automate and standardize the assembly of materials, where properties are defined across scales by combining top-down specification via additive manufacturing with bottom-up pattern formation via molecular self-organization.…”

Synthetic spatial patterning in bacteria: advances based on novel diffusible signals

“…Biological patterning can be defined as the organized arrangement of an organism’s features (Davies, 2017), where an initially uniform field of cells gains complexity and heterogeneity in the spatial domain (Murray, 2013; Davies and Glykofrydis, 2020). This structure is crucial for function in multicellular organisms (Blest, 1957; Stevens et al ., 2006; Strauss et al ., 2020).…”