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Patterning and growth control in vivo by an engineered GFP gradient

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Engineering synthetic morphogens

Morphogens provide positional information during tissue development. For this behavior to occur, morphogens must spread out and form a concentration gradient; however, their mechanism of transport remains a matter of debate. Stapornwongkul et al. now show that in the presence of extracellular binding elements (binders), the inert green fluorescent protein (GFP) can form a detectable concentration gradient by diffusion in the developing fly wing (see the Perspective by Barkai and Shilo). When combining the expression of nonsignaling binders and receptors engineered to respond to GFP, a synthetic GFP gradient can substitute for a natural morphogen to organize growth and patterning. In related work, Toda et al. also show that GFP can be converted into a morphogen by providing anchoring interactions that tether the molecule, forming a gradient that can be recognized by synthetic receptors that activate gene expression. These synthetic morphogens can be used to program de novo multidomain tissue patterns. These results highlight core mechanisms of morphogen signaling and patterning and provide ways to program spatial tissue organization independently from endogenous morphogen pathways.

Science, this issue p. 321, p. 327; see also p. 292

Abstract

Morphogen gradients provide positional information during development. To uncover the minimal requirements for morphogen gradient formation, we have engineered a synthetic morphogen in Drosophila wing primordia. We show that an inert protein, green fluorescent protein (GFP), can form a detectable diffusion-based gradient in the presence of surface-associated anti-GFP nanobodies, which modulate the gradient by trapping the ligand and limiting leakage from the tissue. We next fused anti-GFP nanobodies to the receptors of Dpp, a natural morphogen, to render them responsive to extracellular GFP. In the presence of these engineered receptors, GFP could replace Dpp to organize patterning and growth in vivo. Concomitant expression of glycosylphosphatidylinositol (GPI)–anchored nonsignaling receptors further improved patterning, to near–wild-type quality. Theoretical arguments suggest that GPI anchorage could be important for these receptors to expand the gradient length scale while at the same time reducing leakage.

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How neuron types encode behavioral states

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What is the contribution of molecularly defined cell types to neural coding of stimuli and states? Xu et al. aimed to evaluate neural representation of multiple behavioral states in the mouse paraventricular hypothalamus. To achieve this goal, they combined deep-brain two-photon imaging with post hoc validation of gene expression in the imaged cells. The behavioral states could be well predicted by the neural response of multiple neuronal clusters. Some clusters were broadly tuned and contributed strongly to the decoding of multiple behavioral states, whereas others were more specifically tuned to certain behaviors or specific time windows of a behavioral state.

Science, this issue p. eabb2494

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Fiber tension enables tissue scaling

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Tissue development, homeostasis, and repair require cells to sense mechanical forces. Although many molecular actors implicated in cell mechanosensitivity have been extensively studied, the basis by which cells adapt their mechanical responses to their geometry remains poorly defined. López-Gay et al. now identify how two fundamental epithelial structures—stress fibers and tricellular junctions—endow Drosophila cells with an internal ruler to scale their mechanical response with their area. This work explains how cells of different sizes within an epithelial tissue collectively adapt their mechanical response to control tissue shape and proliferation. Scaling of biological properties with size is a core property of other biological systems.

Science, this issue p. eabb2169

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Species richness maintains mutualisms

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Mutualistic communities of species that benefit each other are ubiquitous in ecosystems and are important for ecosystem functioning. However, the relationship between the persistence of mutualisms and species richness has remained unclear. Vidal et al. used a synthetic mutualism in brewer’s yeast to experimentally test whether species richness buffers mutualistic communities against exploitation by species that do not provide benefits in return. They showed that richer mutualist communities survive exploitation more often than pairwise mutualisms and that higher species richness and functional redundancy allow mutualist communities to persist in the presence of exploiters. These results provide experimental support for the hypothesis that species richness is necessary for the function and maintenance of mutualistic communities.

Science, this issue p. 346

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