Synthetic mammalian pattern formation driven by differential diffusivity of Nodal and Lefty

Sekine, Ryoji; Shibata, Tatsuo; Ebisuya, Miki

doi:10.1038/s41467-018-07847-x

Cited by 83 publications

(43 citation statements)

References 49 publications

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“…Combining cadherin-mediated cell sorting with artificial cell-cell communication also produced multi-layer self-organization and multicellular patterning ( Toda et al., 2018 , 2020 ). Instead Skine et al., showed synthetic mammalian reaction-diffusion patterns via reconstituting Nodal-Lefty network in mammalian cells ( Sekine et al., 2018 ). Future efforts will focus on engineering other morphological motifs such as controlled tube formation and folding ( Cachat et al., 2014 ).…”

Section: Significant Advances So Farmentioning

confidence: 99%

Synthetic living machines: A new window on life

Ebrahimkhani

Levin

2021

iScience

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Summary Increased control of biological growth and form is an essential gateway to transformative medical advances. Repairing of birth defects, restoring lost or damaged organs, normalizing tumors, all depend on understanding how cells cooperate to make specific, functional large-scale structures. Despite advances in molecular genetics, significant gaps remain in our understanding of the meso-scale rules of morphogenesis. An engineering approach to this problem is the creation of novel synthetic living forms, greatly extending available model systems beyond evolved plant and animal lineages. Here, we review recent advances in the emerging field of synthetic morphogenesis, the bioengineering of novel multicellular living bodies. Emphasizing emergent self-organization, tissue-level guided self-assembly, and active functionality, this work is the essential next generation of synthetic biology. Aside from useful living machines for specific functions, the rational design and analysis of new, coherent anatomies will greatly increase our understanding of foundational questions in evolutionary developmental and cell biology.

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Section: Significant Advances So Farmentioning

confidence: 99%

Synthetic living machines: A new window on life

Ebrahimkhani

Levin

2021

iScience

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“…Cells must coordinate their activities across large tissue fields via biochemical, electrical, and physical signals. Synthetic biology approaches have enabled engineers to create artificial morphogen sender/receiver cell relationships on the centimeter scale ( Sekine et al., 2018 ; Toda et al., 2020 ). Integrating such circuits into models of organogenesis could better coordinate initial conditions for subsequent patterning, such as branching morphogenesis or generating repetitive tissues.…”

Section: Engineering Organogenesismentioning

confidence: 99%

Bioengineering in vitro models of embryonic development

2021

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Stem cell-based in vitro models of embryonic development have been established over the last decade. Such model systems recapitulate aspects of gametogenesis, early embryonic development, or organogenesis. They enable experimental approaches that have not been possible previously and have the potential to greatly reduce the number of animals required for research. However, each model system has its own limitations, with certain aspects, such as morphogenesis and spatiotemporal control of cell fate decisions, diverging from the in vivo counterpart. Targeted bioengineering approaches to provide defined instructive external signals or to modulate internal cellular signals could overcome some of these limitations. Here, we present the latest technical developments and discuss how bioengineering can further advance the optimization and external control of stem cell-based embryo-like structures (ELSs). In vitro models combined with sophisticated bioengineering tools will enable an even more in-depth analysis of embryonic development in the future.

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“…Until now, we ignored the role of regulation in the evolution of surface colonization. Regulation, however, plays a critical role in the evolution of multicellularity, because it enables cells to coordinate their properties to the benefit of collective growth or reproduction [20,[62][63][64][65]. Accordingly, in many surface-associated organisms, cells regulate the spatiotemporal expression of adhesion [18,66,67].…”

Section: Evolution Of Regulationmentioning

confidence: 99%

Cryptic surface-associated multicellularity emerges through cell adhesion and its regulation

Gestel

Wagner

2021

PLoS Biol

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The repeated evolution of multicellularity leads to a wide diversity of organisms, many of which are sessile, including land plants, many fungi, and colonial animals. Sessile organisms adhere to a surface for most of their lives, where they grow and compete for space. Despite the prevalence of surface-associated multicellularity, little is known about its evolutionary origin. Here, we introduce a novel theoretical approach, based on spatial lineage tracking of cells, to study this origin. We show that multicellularity can rapidly evolve from 2 widespread cellular properties: cell adhesion and the regulatory control of adhesion. By evolving adhesion, cells attach to a surface, where they spontaneously give rise to primitive cell collectives that differ in size, life span, and mode of propagation. Selection in favor of large collectives increases the fraction of adhesive cells until a surface becomes fully occupied. Through kin recognition, collectives then evolve a central-peripheral polarity in cell adhesion that supports a division of labor between cells and profoundly impacts growth. Despite this spatial organization, nascent collectives remain cryptic, lack well-defined boundaries, and would require experimental lineage tracking technologies for their identification. Our results suggest that cryptic multicellularity could readily evolve and originate well before multicellular individuals become morphologically evident.

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Synthetic mammalian pattern formation driven by differential diffusivity of Nodal and Lefty

Cited by 83 publications

References 49 publications

Synthetic living machines: A new window on life

Synthetic living machines: A new window on life

Bioengineering in vitro models of embryonic development

Cryptic surface-associated multicellularity emerges through cell adhesion and its regulation

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