Abstract
This study reports a proof-of-concept study as a step toward synthetic-biological morphogenesis of tissues. Events in normal animal development usually follow the sequence: patterning → differential gene expression → morphogenesis. A synthetic biological approach to development might follow a similar sequence, with each stage under the control of synthetic biological modules. The authors have constructed and published a synthetic module that drives self-organised patterning of mammalian cell populations into patches of different cell types. Here, as a proof of concept, they extend the self-patterning module with a morphogenetic effector that drives elective cell death in just one cell type. The result is a self-constructing pattern of two cell types, one of which can be selectively eliminated to leave remaining cells as a monolayer with a net-like structure. This simple device demonstrates and validates the idea of coupling synthetic biological morphogenetic effectors to synthetic biological patterning devices. It opens the path to engineering more sophisticated structures and, perhaps eventually, tissues.
Highlights
Synthetic biology constructs allow bio-engineers to endow living cells with properties that originate not in serendipitous evolution but in deliberate design [1,2,3]
Most examples of natural development follow a sequence in which (i) a field of cells becomes patterned, (ii) cells in the different zones defined by the pattern express different sets of genes and (iii) these genes drive morphogenesis, which creates tissue anatomy [19]
One line, ‘E-cells’, produces the cell adhesion molecule, E-cadherin, together with a Green Fluorescent Protein (GFP) reporter, when the cells are incubated in tetracycline
Summary
Synthetic biology constructs allow bio-engineers to endow living cells with properties that originate not in serendipitous evolution but in deliberate design [1,2,3]. Our best model for understanding the self-organisation of tissues is natural embryonic development, in which cells have to organise themselves: there is no external source of information driving the detailed organisation in organisms such as mammals (some other organisms make use of light, gravity and flow to influence broad features, such as the direction of the root–shoot axis of plants). Most examples of natural development follow a sequence in which (i) a field of cells becomes patterned (e.g. by chemical gradients), (ii) cells in the different zones defined by the pattern express different sets of genes and (iii) these genes drive morphogenesis, which creates tissue anatomy [19]. One method for constructing synthetic biological self-assembling structures would be to follow this basic sequence: form a pattern → change gene expression → trigger morphogenesis
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