Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 57,381 bioRxiv papers from 264,204 authors.
Pattern formation is fundamental for embryonic development. Although synthetic biologists have created several patterns, a synthetic mammalian reaction-diffusion pattern has yet to be realized. TGF-β family proteins Nodal and Lefty have been proposed to meet the conditions for reaction-diffusion patterning: Nodal is a short-range activator that enhances the expression of Nodal and Lefty whereas Lefty acts as a long-range inhibitor against Nodal. However, the pattern forming possibility of the Nodal-Lefty signaling has never been directly tested, and the underlying mechanisms of differential diffusivity of Nodal and Lefty remain unclear. Here, through a combination of synthetic biology and theoretical modeling, we show that a reconstituted minimal network of the Nodal-Lefty signaling spontaneously gives rise to a pattern in mammalian cell culture. Surprisingly, extracellular Nodal was confined underneath the cells as small clusters, resulting in a narrow distribution range compared with Lefty. We further found that the finger 1 domain of the Nodal protein is responsible for its short-range distribution. By transplanting the finger 1 domain of Nodal into Lefty, we converted the originally long-range distribution of Lefty to a short-range one, successfully preventing the pattern formation. These results indicate that the differences in the localization and domain structures between Nodal and Lefty, combined with the activator-inhibitor topology, are sufficient for reaction-diffusion pattern formation in mammalian cells.
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